OncologyLive® is the flagship publication of OncLive®. Each issue delivers expert insights and clinical oncology news and updates, which impact the day-to-day clinical practice of oncology professionals who work tirelessly to help improve patient outcomes.

Pancreatic ductal adenocarcinoma (PDAC) is a notoriously lethal malignancy, due in large part to the fact that it is often diagnosed once unresectable and/or metastatic. When PDAC is found at potentially resectable stages, however, long-term cure is increasingly possible, particularly with improvements in neoadjuvant and adjuvant therapies.

 Although they account for a relatively small fraction of all PDAC cases, those with stage I PDAC have particularly favorable outcomes, with recent data demonstrating 5-year overall survival rates of 83.7% and 74.3% for stage IA and IB PDAC, respectively.

 For individuals with known significant familial and/or germline risk factors for PDAC (

), such data naturally raise the question as to whether surveillance and early detection of PDAC could help improve outcomes from this typically deadly malignancy.

In recent years, there has been a growing body of literature investigating imaging-based PDAC surveillance using endoscopic ultrasound (EUS) and/or magnetic resonance cholangiopancreatography (MRCP) in those with significantly increased genetic and/or familial risk. These data have suggested at least a potential for such surveillance to detect PDAC at earlier, potentially resectable stages, compared with historical controls.

 Such encouraging findings are counterbalanced by the fact that cystic pancreatic lesions—mostly presumed side branch intraductal papillary mucinous neoplasms—are exceptionally common findings in this high-risk population, highlighting the very real potential for overtreatment of these otherwise low-risk lesions, especially given the significant anxiety often inherent to having significant genetic/familial PDAC risk.

 Additionally, with  the relatively short-term follow-up in these early efforts, one reasonable critique was that the promising outcomes simply reflected lead-time bias, given the absence of unscreened control groups. 

Most recently, the Cancer of the Pancreas Screening (CAPS) consortium analyzed prospective data from 1731 high-risk individuals undergoing imaging-based surveillance with MRCP and/or EUS, forming an aggregate of 5041 person-years of follow-up, which provided important longer-term insights into the potential benefits of such surveillance.

 These newest prospective CAPS data demonstrated an impressive “number needed to screen,” with 1 PDAC identified per year for every 194 high-risk individuals screened.9 Screen-detected PDACs were disproportionately early stage (58%, stage I; 16%, stage II) whereas PDACs diagnosed in study participants who had been lost to follow-up were not (86%, stage IV).

 Most critically, high-risk individuals with screen-detected PDAC had exceedingly good long-term outcomes with a 5-year overall survival rate of 73.3% (vs 0.0% for participants with PDAC diagnosed after being lost to follow-up) and median 9.8-year overall survival (vs median 1.5 years in those lost to follow-up; unadjusted HR, 0.13; 95% CI, 0.03-0.50).

These data are still limited by the lack of unscreened control populations; however, these results seem to strongly refute the notion of lead-time bias being solely responsible for the very promising outcomes, given the massive difference compared with historical data. As such, guidelines from the National Comprehensive Cancer Network (NCCN) recommend imaging-based surveillance for many individuals with familial and/or genetic high risk for PDAC with annual MRCP and/or EUS (

However, several important questions remain regarding how to transform these successes from multicenter clinical trials into routine clinical care for individuals at risk for PDAC.

 One critical unknown is whether these promising outcomes can be replicated outside of a clinical trial setting. Both the performance and interpretation of MRCPs and EUSs can be quite specialized and nuanced, and the decision to monitor vs intervene on potentially worrisome imaging findings should ideally be made in the context of experienced multidisciplinary expertise that is not broadly available, which clearly limits the scalability of imaging-based PDAC surveillance and introduces the very real possibility of disparities in access to such care.

Another unanswered question is whether current criteria are too restrictive as to which high-risk individuals should be considered for imaging-based surveillance. For most of the variants and genetic syndromes that predispose to PDAC (

, and Lynch syndrome), current NCCN guidelines recommend imaging-based surveillance beginning at age 50 years (or 10 years younger than the earliest PDAC in the family), but only if there is a known first- and/or second-degree relative with PDAC.

 This family history requirement is based on the fact that the various CAPS studies have only evaluated individuals with germline predisposition who also had a family history of PDAC, rather than any data conclusively showing that a family history of PDAC further increases risk.

 Some preliminary data have suggested that the yield of imaging-based PDAC surveillance may be comparable in individuals with germline PDAC risk who lack a PDAC family history vs what has been seen in those with a family history, raising the question as to whether all such individuals should be screened.

 To that end, recent clinical practice guidelines from the American Society for Gastrointestinal Endoscopy recently endorsed imaging-based surveillance for all individuals with pathogenic germline variants in 

, regardless of family history (beginning at age 50 years), albeit as a “conditional recommendation” based on “very low quality of evidence.”

Lastly, the intriguing question of how to use novel blood-based approaches to screening and early cancer detection looms large. Certainly, the hypothetical possibility of effective blood-based assay for PDAC surveillance would hold tremendous appeal and would certainly address the issues of scalability and subjectivity that are inherent to imaging-based surveillance. Various such assays are beginning to be studied,

 yet their ability to effectively, prospectively screen for PDAC in asymptomatic individuals (whether high or average risk) remains unproven. Currently, the use of such blood-based assays is not endorsed by NCCN guidelines or other professional societies for PDAC surveillance.

In sum, recent years have brought tremendous progress in demonstrating that there is hope for improving mortality from PDAC through early detection. Although challenges and questions remain regarding how, where, and whom to screen for PDAC, the real-world successes from the CAPS studies and other such efforts provide well-justified optimism that we can continue to improve outcomes from this disease.

Conroy T, Hammel P, Hebbar M, et al; Canadian Cancer Trials Group and the Unicancer-GI–PRODIGE Group. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. 

. 2018;379(25):2395-2406. doi:10.1056/NEJMoa1809775

Blackford AL, Canto MI, Klein AP, Hruban RH, Goggins M. Recent trends in the incidence and survival of stage IA pancreatic cancer: a Surveillance, Epidemiology, and End Results analysis. 

. 2020;112(11):1162-1169. doi:10.1093/jnci/djaa004

NCCN. Clinical Practice Guidelines in Oncology. Genetic/ familial high-risk assessment: breast, ovarian, and pancreatic, version 3.2023. Accessed June 7, 2023. https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf

Yurgelun MB. Building on more than 20 years of progress in pancreatic cancer surveillance for high-risk individuals. 

. 2022;40(28):3230-3234. doi:10.1200/JCO.22.01287

Canto MI, Almario JA, Schulick RD, et al. Risk of neoplastic progression in individuals at high risk for pancreatic cancer undergoing long-term surveillance. 

. 2018;155(3):740-751.e2. doi:10.1053/j.gastro.2018.05.035

Vasen H, Ibrahim I, Ponce CG, et al. Benefit of surveillance for pancreatic cancer in high-risk individuals: outcome of longterm prospective follow-up studies from three European expert centers. 

. 2016;34(17):2010-2019. doi:10.1200/JCO.2015.64.0730

Canto MI, Hruban RH, Fishman EK, et al; American Cancer of the Pancreas Screening (CAPS) Consortium. Frequent detection of pancreatic lesions in asymptomatic high-risk individuals. 

. 2012;142(4):796-804; quiz e14-15. doi:10.1053/j.gastro.2012.01.005

Konings IC, Harinck F, Kuenen MA, et al; Dutch research group on pancreatic cancer surveillance in high-risk individuals. Factors associated with cancer worries in individuals participating in annual pancreatic cancer surveillance. 

. 2017;16(1):143-151. doi:10.1007/s10689-016-9930-4

Dbouk M, Katona BW, Brand RE, et al. The multicenter Cancer of Pancreas Screening study: impact on stage and survival. 

. 2022;40(28):3257-3266. doi:10.1200/JCO.22.00298

Katona BW, Long JM, Ahmad NA, et al. EUS-based pancreatic cancer surveillance in 

 carriers without a family history of pancreatic cancer. 

. 2021;14(11):1033-1040. doi:10.1158/1940-6207.CAPR-21-0161

Calderwood AH, Sawhney MS, Thosani NC, et al. American Society for Gastrointestinal Endoscopy guideline on screening for pancreatic cancer in individuals with genetic susceptibility: methodology and review of evidence. 

. 2022;95(5):827-854.e3. doi:10.1016/j.gie.2021.12.002

Brand RE, Persson J, Bratlie SO, et al. Detection of early-stage pancreatic ductal adenocarcinoma from blood samples: results of a multiplex biomarker signature validation study. 

. 2022;13(3):e00468. doi:10.14309/ctg.0000000000000468

Articles

Recent years have brought tremendous progress in demonstrating that there is hope for improving mortality from pancreatic ductal adenocarcinoma through early detection.

Updates on Imaging-Based Pancreatic Cancer Surveillance for Individuals With Increased Genetic and Familial Risk

Efforts to develop the first FDA-approved agent specifically for patients with primary central nervous system lymphoma (PCNSL) have been initiated with the phase 2 PROSPECT trial (NCT04947319).

“PCNSL is an extremely rare disease; it accounts for [approximately] 3% to 4% of malignant central nervous system [CNS] tumors,” Lakshmi Nayak, MD, the director of the Center for Central Nervous System (CNS) Lymphoma, a senior physician at Dana-Farber Cancer Institute, and an assistant professor of neurology at Harvard Medical School, in Boston, Massachusetts, said in an interview with 

. “The diagnosis is typically made when patients present with neurologic symptoms and an MRI [of the] brain or is performed. There are certain characteristics that are suggestive of primary CNS lymphoma or CNS lymphomas in general in the brain; however, we always recommend histopathologic confirmation to make the diagnosis. In general, this is a disease of older people; the median age of diagnosis is [approximately] 65 years.”

PCNSL is a highly aggressive form of extranodal non-Hodgkin lymphoma that is typically confined to the brain, eyes, and cerebrospinal fluid, and does not usually display evidence of systemic spread. A favorable response to both chemotherapy and radiotherapy is typical, but survival is still inferior compared with lymphomas occurring outside of the CNS. Additionally, if a patient fails frontline therapy, the prognosis is poor.

PROSPECT will evaluate the second-generation Bruton tyrosine kinase (BTK) inhibitor tirabrutinib (formerly ONO-4059) in patients with PCNSL. Tirabrutinib is a selective agent that can be given orally once daily and has previously displayed clinical activity in patients with relapsed or refractory B-cell malignancies. The agent binds irreversibly and covalently to BTK Cys-481, with significantly greater selectivity for EGFR, ITK, and BMX compared with the first-generation BTK inhibitor ibrutinib (Imbruvica).

The FDA granted tirabrutinib orphan drug designation on March 21, 2023, for the treatment of patients with PCNSL. Outside the United States, the agent has received approval for relapsed or refractory PCNSL in Japan, South Korea, and Taiwan, in March 2020, November 2021, and February 2022, respectively.

Tirabrutinib has previously shown efficacy as monotherapy for patients with relapsed or refractory PCNSL in a Japanese phase 1/2 trial (JapicCTI-173646). The study enrolled patients 20 years or older with a cerebral lesion over 1 cm in the longest diameter identified via gadolinium-enhanced nuclear MRI within 2 weeks of the first dose of tirabrutinib. Patients also needed to have a life expectancy of at least 3 months and a Karnofsky performance status (KPS) of 70 to 100 to be eligible for enrollment. Patients without a B-cell neoplasm, those who received a corticosteroid within 14 days prior to the first dose of tirabrutinib, and those with infectious diseases were excluded.

In phase 1, oral tirabrutinib evaluated during a dose-limiting toxicity (DLT) period of 28 days. The agent was administered at a dose of 320 mg daily in cohort 1 and 480 mg daily in cohort 2. In phase 2, the agent was given at the dose determined in phase 1 for 1 cycle.

The primary efficacy end point was overall response rate (ORR) assessed by central independent review committee (IRC). Adverse effects (AEs), complete response (CR) rate, best overall response (BOR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were all also assessed.

At the June 13, 2019, data cutoff, 20 patients were treated with tirabrutinib 320 mg and 24 patients with tirabrutinib 480 mg. The median age of all enrolled patients was 60 years (range, 29-86) and the median KPS was 80 (range, 70-100). Most patients were men (54.5%), had relapsed disease (75.0%), had undergone whole-brain radiotherapy (65.9%), and had had previous treatment with rituximab (Rituxan; 59.1%). All patients had previously received high-dose methotrexate and the median number of prior therapies for PCNSL was 2 (range, 1-14).

Findings from the phase 1 portion of the study showed that the ORR by central IRC was 63.6% (95% CI, 47.8%-77.6%), including a CR rate of 34.1% (95% CI, 20.5%-49.9%), among all patients (N = 44). The median PFS was 2.9 months (95% CI, 1.8-11.1).5 More specifically, patients treated at the 320-mg dose level achieved an ORR of 60.0% (95% CI, 36.1%-80.9%), with a CR rate of 25.0% (95% CI, 8.7%-49.1%). The median PFS was 2.1 months (95% CI, 1.8-not estimable [NE]).

Notably, patients who received the 480-mg dose (n = 7) experienced an ORR of 100% (95%, 59.0%-100%), including a 57.1% (95% CI, 18.4%-90.1%) CR rate and a median PFS of 11.1 months (95% CI, 1.4-NE). Among those treated at this dose on an empty stomach (n = 17), the ORR was 52.9% (95% CI, 27.8%-77.0%), the CR rate was 35.3% (95% CI, 14.2%-61.7%), and the median PFS was 5.8 months (95% CI, 1.0-5.8).

“The response rate was very profound,” Nayak said. “[According to] long-term data, it seems that there’s a reasonable [number] of patients that tend to have long-term remission. Of course, we need longer follow-up and we’re waiting to see how the drug performs in our population.” Safety data revealed that any-grade AEs occurred at a rate of 58.8% in the overall population, with 47.7% being of grade 3 or greater severity. The most common any-grade AEs were rash (31.8%), neutropenia (22.7%), leukopenia (18.2%), and lymphopenia (15.9%). Commonly reported grade 3 or higher AEs were neutropenia (9.1%), lymphopenia (6.8%), leukopenia (6.8%), and erythema multiforme (6.8%).

Serious AEs occurred 13 times in 9 patients, including 8 adverse drug reactions in 6 patients. Treatment with tirabrutinib was discontinued because of AEs in 3 patients. One death attributed to an AE was reported.

“We expected an AE profile that would be slightly different and better than the first-generation [BTK inhibitors],” Nayak said. “[We saw] a fair number of patients that experience rashes—that seems to be the most common AE—[and] the majority of these rashes can be managed. Patients [also] developed neutropenia with a risk for infections. The risk is there, but the high-risk infections are uncommon with this drug. They did not see cardiac toxicities. One of the concerns with BTK inhibitors is the possibility of its effect on developing cardiac arrhythmias, the most common [being] atrial fibrillation.”

No DLTs were reported in phase 1 and the maximum-tolerated dose was not reached. Thus, the recommended phase 2 dose was 480 mg. However, the dose for phase 2 was reduced to 320 mg because of the presence of 3 grade 3 skin-related AEs and the only death—which was attributed to pneumocystis jirovecii pneumonia and interstitial lung disease—were observed at the 480-mg dose level. However, investigators added that 2 other clinical studies showed treatment with tirabrutinib to be safe and tolerable at a dose of 480 mg under fasted conditions.

PROSPECT is a nonrandomized, parallel assignment trial that will evaluate the efficacy, safety, and pharmacokinetics of tirabrutinib monotherapy for adult patients with relapsed or refractory PCNSL in part A. In part B of the study, tirabrutinib will be examined in combination with methotrexate/ temozolomide/rituximab or rituximab/methotrexate/procarbazine/ vincristine for the treatment of adult patients with newly diagnosed treatment-naïve PCNSL.

In part A, patients will receive oral tirabrutinib at 480 mg once daily on an empty stomach until disease progression or unacceptable toxicity. Part B will evaluate oral tirabrutinib at a dose of 320 mg or 480 mg in combination with an induction regimen of either methotrexate/ temozolomide/rituximab or rituximab/ methotrexate/procarbazine/vincristine. Induction regimens will continue for four 28-day cycles or until disease progression or unacceptable toxicity.

To be eligible for either part A or part B, patents must have an ECOG performance status of 2 or less, a measurable brain lesion with a minimum diameter of over 1 cm, and adequate bone marrow, renal, and hepatic function. A life expectancy of at least 3 months is mandatory in the monotherapy arm and at least 6 months is required in the combination arms. Patients with intraocular PCNSL without a brain lesion, those with non–B-cell PCNSL, and those who have undergone prior treatment with a BTK inhibitor will not be eligible for the study.

The primary end point in part A of the PROSPECT trial is ORR. In part B, the coprimary end points are AEs, CR rate, and estimating the dose of tirabrutinib in combination with each backbone induction regimen based upon AEs, serious AEs, and toxicities reported during the initial cycle of induction therapy in the dose-ranging phase. Secondary end points include DOR, time to response, and best overall response. The study is recruiting patients, with a target enrollment of approximately 112 participants, and is estimated to be completed in July 2026.

“[PCNSL] is a rare disease, but it’s very treatable,” Nayak said. “Having said that, there is tremendous amount of work that [still] needs to be done. The number of clinical trials that are currently available for [patients with] PCNSL in the past few years has increased tremendously. Options remain, [but] we need to solidify our upfront regimen so that we can get to a cure, which I believe is possible in this disease with the right treatments.”

Oncology Live®

Efforts to develop the first FDA-approved agent specifically for patients with primary central nervous system lymphoma have been initiated with the phase 2 PROSPECT trial.

PROSPECT Trial Looks to Add Effective Option  for Patients With R/R PCNSL

Despite the high prevalence of KRAS mutations in pancreatic cancers, a limited number of cases harbor an actionable point mutation.

Unlike other tumors where variants in KRAS, such as G12C, are more prominent,

explorations into the more common subtypes in pancreatic cancer have begun to provide more guidance for therapeutic development as significant differences in survival outcomes come to light.

The most common KRAS mutations in patients with pancreatic ductal adenocarcinoma (PDAC) are found in the G12 codon. Occurring in up to 44% of patients, G12D is the most common mutational substitution, with G12V (34%) and G12R (20%) having the second and third highest incidence.5 Unfortunately, although G12C has been shown to improve outcomes when targeted with KRAS G12C inhibitors, such as adagrasib (Krazati) and sotorasib (Lumakras), this target is only actionable in up to 3% of patients with PDAC.

A recent undertaking by investigators sought to characterize prognostic and molecular differences among variants G12D and G12R. Findings were presented at the 2023 American Society for Clinical Oncology (ASCO) Annual Meeting.

In the updated 2023 analysis, the investigators leveraged data from a genomic database to analyze immune marker prevalence and variant expression in KRAS, as well as assess survival outcomes from claims data among those with KRAS-mutant PDAC.

The identified mutations in the subset were G12R (n = 621), G12V (n = 1294), G12C (n = 74), and G12D (n = 1766).3 These groups had similar median ages of 68, 67, 66, and 67 years, respectively. Immune checkpoint marker prevalence findings showed that 23.5% of those with G12Cmutant disease were PD-L1 positive via the VENTANA PD-L1 (SP142) immunohistochemistry (IHC) assay. Among those with G12D-, G12V-, and G12R-mutant disease, the rates of IHC PD-L1 positivity were 19.0%, 14.2%, and 13.0%, respectively.

Tumor mutational burden was also assessed with low rates of positivity noted across the groups at 2.7%, 1.0%, 1.4%, and 1.1%, for the G12C, G12D, G12V, and G12R groups, respectively.3 Mismatch repair deficient and microsatellite instability–high disease was noted in 1.4%, 0.9%, 1.0%, and 0.6% of patients in these subgroups, respectively.

A comparison of overall survival (OS) outcomes were reported for G12R (n = 890) vs G12D (n = 2604), as well as for G12V (n = 1836) vs G12D. For G12R vs G12D, the median OS was 396 days (95% CI, 361-425) vs 311 days (95% CI, 294-329), for a median difference of 85 days (HR, 0.809; 95% CI, 0.743-0.880; P < .00001). For patients with G12V-mutant disease, the median OS was 362 days (HR, 0.911; 95% CI, 0.854-0.972; P = .005), with a median difference of 51 days compared with patients with G12Dmutant disease.

Study authors noted that “metformin appeared to impact survival in the KRAS G12R subgroup.” 

The tumor microenvironment also revealed that B cell, M2 macrophages, and CD8+ T-cell infiltration trended higher in patients with G12R-mutant disease vs G12D (P < .05). The false discovery rate adjusted P value (q) was used to compared CD4+ T-cell infiltration and showed a trend toward higher rates in the G12Rmutant group vs G12D-mutant group (q < .05).

Another approach to leveraging KRAS variants is through vaccination. Specifically, an investigational KRAS-targeted vaccine, ELI-002, has been designed to engage lymph node–specific activity and encourage the lasting potency of these agents.

At the 2023 ASCO meeting, preliminary results from the AMPLIFY-201 trial (NCT04853017) were presented for the 2-peptide formulation of the vaccine product. Specifically, the agent is a 3-component lymph node–targeting amphiphile cancer vaccine comprising KRAS G12D- and G12R-modified peptide antigens and a toll-like receptor 9 (TLR9) agnostic DNA adjuvant.

 The amphiphile ligands were previously assessed as a modification method in solid tumor chimeric antigen receptor (CAR) T-cell therapy for solid tumors.

The modified cells targeted lymph nodes and primed CAR T cells in the lymph node microenvironment, resulting in expansion in murine models.

“Conventional vaccine components [eg, peptide antigens and molecular adjuvants] are rapidly absorbed into blood capillaries after administration, leading to poor delivery to lymph nodes, where protective immune responses are orchestrated,” Eileen M. O’Reilly, MD, and coinvestigators wrote in findings from the study. “Amph-modification promotes albumin binding to reprogram vaccines for enhanced lymph node delivery, resulting in coordinated transport of antigen and adjuvant to immune cells. Improved uptake by antigen-presenting cells results in enhanced antigen presentation and co-stimulation to cognate T cells. Restricted delivery to lymph nodes prevents systemic exposure to avoid toxic effects of potent adjuvants.” O’Reilly is the Winthrop Rockefeller Endowed Chair of Medical Oncology, codirector of medical initiatives at the David M. Rubenstein Center for Pancreatic Cancer Research, and section head of hepatopancreaticobiliary and neuroendocrine cancers at Memorial Sloan Kettering Cancer Center in New York, New York. She is also the 2023 Giants of Cancer Care® award winner in the gastrointestinal cancer category.

Prior to enrollment in the AMPLIFY-201 study, patients needed to have received locoregional therapy, including surgery plus neoadjuvant/ adjuvant chemotherapy. During the screening period, 92 patients were assessed for mutant KRAS variants of either G12R or G12D, imaging for no evidence of disease, and analysis for minimal residual disease status confirmed by either circulating tumor DNA (ctDNA) positivity or positive serum biomarker. The most common reason for noninclusion was ctDNA, CA19-9 level, or carcinoembryonic antigen (CEA) negativity (n = 40).

Twenty-five patients—20 with PDAC and 5 with colorectal cancer (CRC)—were enrolled across 5 cohorts. All patients received a fixed dose of the KRAS G12D/G12R-modified peptide (AmphPeptides 2P) at 1.4 mg. Ascending doses of the TLR9 agnostic DNA adjuvant (Amph-CPG-7909) were administered as follows: 0.1 mg (cohort 1; n = 3), 0.5 mg (cohort 2; n = 6), 2.5 mg (cohort 3; n = 5), 5.0 mg (cohort 4; n = 5), and 10.0 mg (cohort 5; n = 6).4 Of note, no patients with CRC were enrolled in cohorts 3 or 5. 

Overall, the median age was 61 years (range, 37-77), and 60% of participants were women. The median BMI was 23.4 kg/m2 (range, 16.0-38.0). Most patients were White (84.0%) and had an ECOG performance status of 0 (72.0%). At screening, most patients had stage III/IV disease (68.0%). All patients had prior systemic therapy and surgery, with 28% of patients also having received radiation therapy.

The prime immunization period was week 0 through 7, with dosing occurring on weeks 0, 1, 2, 3, 5, and 7. No doses were administered on weeks 8 through 17. The booster immunization period occurred on weeks 17 through 25, with doses administered on weeks 20, 21, 22, and 23. The follow-up period concluded at week 105. Serum biomarkers were assessed at baseline, week 17, week 25, and week 105, with ctDNA assessments conducted at baseline, between weeks 2 and 3, between weeks 5 and 6, week 17, week 20, weeks 24 and 25, and at the end of the follow-up period.

The primary end points of the study are safety, tolerability, and recommended phase 2 dose. Secondary end points include tumor biomarker reduction and clearance assessing the ctDNA and/or CA19-9 or CEA expression. Finally, investigators identified immunogenicity and relapse-free survival (RFS), using RECIST 1.1 criteria as exploratory end points. At data cutoff, follow-up was ongoing for biomarker response, duration of response, RFS, and OS.

Early discontinuation was reported as follows: cohort 1 (n = 2), cohort 2 (n = 4), cohort 3 (n = 3), cohort 4 (n = 2), cohort 5 (n = 2). In cohort 4, one patient remained on treatment, at a median follow-up of 17.3 weeks; and 4 patients in cohort 5 remained on treatment, with a median follow-up of 13.0 weeks. The remainder of the patients completed treatment. No patients experienced dose-limiting toxicities, grade 3 or higher, serious treatment-related adverse events (AEs), or cytokine release syndrome events. Additionally, investigators reported that injection-site reactions reported for 3 patients were grades 1 and 2. Further, an increase in AEs was not observed with dose escalation of Amph-CpG-7909.

The best overall biomarker response from baseline was 77% (n = 17 of 22), and clearance of ctDNA was reported in 32% of patients (n = 7 of 22). Of note, mutant KRAS-specific T-cell responses were observed with an average 56-fold increase (range, 2-423). In pancreatic tumors, T-cell infiltration was 10- to 29-fold higher than previously reported in pancreatic literature, according to investigators.

 CD4 and CD8 T-cell responses were observed, with 50% of patients demonstrating mixed responses, 13% having only CD8 responses, and 38% having only CD4 responses. Finally, investigators reported that patients generated broad responses targeting multiple mutant KRAS antigens beyond G12D and G12R, with 10% of patients having 1 antigen response, 25% of patients have a response of 2 to 4 antigens, 30% having a response of 5 to 6 antigens, and 35% having a response of 7 antigens.

In an analysis of a pancreatic tumor receiving the 2.5-mg dose of Amph-CpG-7909, investigators identified that ctDNA increased prior to radiographic relapse, and that PD-L1 expression of 10% was noted in this sample, possibly suggesting that this may be a mechanism of resistance for ELI-002.

AMPLIFY-7P, a phase 1/2 study (NCT05726864) evaluating a 7-peptide formulation of ELI-002, has been initiated to evaluate the construct against 7 of the most common KRAS mutations. The expansive targets may have implications for several solid tumors, and next steps include pursuing the efficacy of the vaccination for patients with cancers such as non–small cell lung cancer, CRC, PDAC, or those with mutations in KRAS G12D, G12R, G12V, G12A, G12C, G12S, G13D, G12D, or NRAS G12R, G12V, G12C, or G12S.

Both studies presented at the 2023 ASCO meeting shine additional light on the untapped potential of the previously deemed untargetable KRAS mutation.

 As more is understood about the biology of PDAC tumors, targeting common KRAS variants in these tumors following exhaustion of all curative intent surgery, chemotherapy, and radiation ushers in a novel postadjuvant setting for investigators.

With advances in developing point mutation–specific treatments, such as adagrasib and sotorasib, for the treatment of patients with KRAS G12C–mutant lung cancer, its early days to judge how effective efforts to unpack the variety of variants that are actionable for patients with pancreatic cancer.

Clinicians referring a patient to MSK can do so by visiting msk.org/refer, emailing referapatient@mskcc.org, or by calling 833-315-2722.

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FDA grants accelerated approval to adagrasib for KRAS G12C-mutated NSCLC. FDA. December 12, 2022. Accessed June 15, 2023. bit.ly/3XxOuNH 

Ardalan B, Ciner A, Baca Y, et al. Not all treated KRAS-mutant pancreatic adenocarcinomas are equal: KRAS G12D and survival outcome. J Clin Oncol. 2023;41(suppl 16):4020. doi:10.1200/ JCO.2023.41.16_suppl.4020 

O’Reilly EM, Wainberg ZV, Weekes CD, et al. AMPLIFY-201, a first-in-human safety and efficacy trial of adjuvant ELI-002 2P immunotherapy for patients with high-relapse risk with KRAS G12D- or G12R-mutated pancreatic and colorectal cancer. J Clin Oncol. 2023;41(suppl 16):2528. doi:10.1200/JCO.2023.41.16_suppl.2528 

Diehl AC, Hannan LM, Zhen DB, et al. KRAS mutation variants and co-occurring PI3K pathway alterations impact survival for patients with pancreatic ductal adenocarcinomas. Oncologist. 2022;27(12):1025-1033. doi:10.1093/oncolo/oyac179

Hong DS, Fakih MG, Strickler JH, et al. KRASG12C inhibition with sotorasib in advanced solid tumors. N Engl J Med. 2020;383(13):1207-1217. doi:10.1056/NEJMoa1917239 

Elicio Therapeutics announces positive interim data from the phase 1 study of an investigational therapeutic cancer immunotherapy, ELI-002, in patients with high relapse risk pancreatic and colorectal cancer at the ASCO Annual Meeting. Elicio Therapeutics. June 3, 2023. Accessed June 25, 2023. bit.ly/3Xrf2Bk 

Ma L, Dichwalkar T, Change JYH, et al. Enhanced CAR-T cell activity against solid tumors by vaccine boosting through the chimeric receptor. Science. 2019;365(6449):162-168. doi:10.1126/science. aav8692 

A study of ELI-002 7P in subjects with KRAS/NRAS mutated solid tumors (AMPLIFY-7P). ClinicalTrials.gov. Updated June 26, 2023. Accessed June 27, 2023. https://classic.clinicaltrials.gov/ct2/ show/NCT05726864 

Jänne PA, Riely GJ, Gadgeel SM, et al. Adagrasib in non-smallcell lung cancer harboring a KRASG12C mutation. N Engl J Med. 2022;387(2):120-131. doi: 10.1056/NEJMoa2204619 

FDA grants accelerated approval to sotorasib for KRAS G12C mutated NSCLC. News release. FDA. May 28, 2021. Accessed June 27, 2023. bit.ly/2ZMCwY8

As more is understood about the biology of PDAC tumors, targeting common KRAS variants in these tumors following exhaustion of all curative intent surgery, chemotherapy, and radiation ushers in a novel postadjuvant setting for investigators.

Explorations Unearth New Potential of KRAS Mutations in Pancreatic Cancer

Therapeutic options for the treatment of patients with multiple myeloma (MM) are growing across the spectrum of care, with recent clinical findings shedding new light on the optimal use of combination regimens and paving the way for another generation of novel therapies, according to a panel of experts.

, leading investigators in the MM field discussed the latest clinical trial findings, many of which were presented during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting in June. The wide-ranging discussion featured insights into selecting combination regimens, with and without transplant, for patients with newly diagnosed MM, and the breadth of exciting novel agents in the pipeline in the relapsed/refractory space.

The panelists were most enthusiastic about the prospects for integrating immunotherapeutic options, such as bispecific antibodies and chimeric antigen receptor (CAR) T-cell therapies, into the MM paradigm.

“I think about the time that I’ve been [treating patients with] myeloma, going from transplant, doublets, triplets, and now quadruplets,” Elizabeth “Betsy” O’Donnell, MD, said. “Now we have this whole expansive field of immunotherapy. I am excited for where we are now in terms of the options we have, but I’m even more excited for the future of how we take these tools and really start to cure [patients] and take that next step in the next 5 to 10 years.”

“I’m excited about incorporating some of these novel immunotherapies in a way that we can really start to think about deeply controlling myeloma and talking about fixed-duration therapy,” Susan Bal, MD, said. “That’s an area that is important to patients. They value that and therefore [it should be] important to all of us.”

At the same time, the development of these therapies shows how “complex and unbelievably multifaceted myeloma is,” Joshua Richter, MD, who served as program moderator, said. He encouraged oncologists treating patients in community settings to contact specialists at academic centers to discuss potential options, even if the patient is not referred for care.

The changes that will be necessary are similar to those that have taken place since daratumumab (Darzalex) became the first monoclonal antibody that the FDA approved for MM in 2015,

 O’Donnell said. Community practices initially referred patients to centers for the first several doses of daratumumab therapy before gaining expertise with the agent.

“There has to be an evolution of practice,” O’Donnell said. “… All these new therapies, [although they are] so exciting, [they] are [also] really the province of academic centers. And that’s a challenge as we develop therapy within myeloma—because we’re making great therapies, but they’re not necessarily accessible to everybody. I do think we have to have an eye on how we [can] get these things back into the community so we have equity and access.”

Although autologous stem cell transplant (ASCT) remains a linchpin of treatment for eligible patients newly diagnosed with symptomatic MM,

 there is considerable controversy over when and how to use transplant, O’Donnell said. She noted that the addition of monoclonal antibodies to frontline therapy has resulted in a “tremendous depth of response” in progression-free survival (PFS), although not necessarily in overall survival (OS), prompting some patients to defer transplant.

Natalie S. Callander, MD, sees a continuing role for ASCT, citing PFS findings from the phase 3 DETERMINATION study (NCT01208662) in patients with newly diagnosed MM. The study tested triplet therapy with lenalidomide (Revlimid), an immunomodulatory drug (IMiD); bortezomib (Velcade), a proteasome inhibitor (PI); and dexamethasone, a corticosteroid (RVd) compared with RVd plus ASCT with high-dose melphalan.

The median PFS was 46.2 months among patients who received RVd vs 67.5 months for participants treated with RVd plus ASCT (HR, 1.53; 95% CI, 1.23-1.91; 

 < .001). For patients with standard-risk MM, the median PFS was 53.2 months with RVd alone vs 82.3 months with RVD plus ASCT (HR, 1.38; 95% CI, 1.07-1.79).

“There is nothing else out there that has given a PFS that long, particularly in standard-risk patients,” Callander said. “I feel very confident about recommending that to patients. We also would agree that with our high-risk patients, that’s an option we very much want them to consider.”

For patients who are candidates for ASCT, there are multiple induction regimens that clinicians can consider as primary therapy. These include regimens based on the CD38-directed monoclonal antibodies daratumumab and isatuximab-irfc (Sarclisa).

Recently reported data help illuminate regimens for transplant-eligible patients with newly diagnosed MM. The phase 2 GRIFFIN trial (NCT02874742) evaluated the induction combination of daratumumab added to RVd (D-RVd). Investigators presented findings from the final analysis at the 19th International Myeloma Society Annual Meeting in August 2022.

After a median follow-up of 49.6 months, patients who received D-RVd (n = 104) experienced a reduction of 55% in the risk of disease progression or death (HR, 0.45; 95% CI, 0.21-0.95; 

 = .0324) compared with participants who received RVd (n = 103). The estimated 48-month PFS rates were 87.2% vs 70.0%, respectively.

The GRIFFIN results inform several important factors, Alfred Garfall, MD, said. “There was no safety signal that should make us concerned about adding daratumumab or using a quadbased induction. These patients do get into autologous stem cell collection and transplant. Even though there does seem to be a little bit of a decreased stem cell yield—maybe a little more difficulty collecting—it doesn’t preclude transplant in anybody.

“You might have to hold the daratumumab a little longer to get the stem cells collected, but it’s not going to preclude that transplant option,” Garfall said. “Even though we’re not using this universally for our patients, we’re very comfortable using it when we think we need it in patients we’re worried about. I could easily see this becoming the standard.”

The single-arm phase 2 MASTER trial (NCT03224507) evaluated a quadruplet similar to that used in GRIFFIN, combining daratumumab with carfilzomib (Kyprolis), a different PI, plus lenalidomide and dexamethasone (Dara-KRd) in patients with newly diagnosed MM. Participants received Dara-KRd induction therapy, followed by autologous hematopoietic cell transplantation, and Dara-KRd consolidation, with treatment ending for patients who reached negative minimal residual disease (MRD) in 2 consecutive assessments.

At a median follow-up of 25.1 months, the MRD negativity rate (< 10

) in 118 evaluable patients was 80% following transplant, including a 66% rate of patients with an MRD of less than 10

. Additionally, the 2-year PFS rate was 87% and the 2-year OS rate was 94%.

“These are very encouraging data for transplant [-eligible patients],” Bal, who is among the study coauthors, said. “Of course, it needs to be carefully weighed against the patient’s preferences and all of the other things we know of [ASCT], but it was great to still see the benefit of alkylators [melphalan] in this setting.”

Nevertheless, the 2-year PFS differed when patients were stratified for the presence of high-risk cytogenetic abnormalities. PFS was 91% and 97%, respectively, for patients with 0 or 1 abnormality but significantly inferior at 58% among participants with 2 or more high-risk factors (

 < .001). The trial defined high-risk features as the gain or amplification of 1q21 and t(14;20) or abnormalities in t(4:14), t(14;16), and del(17p).

Callander, who helped design the MASTER study, said that participants with a 1q alteration plus another aberration seemed to have the worst outcomes. “They went into remission, they were MRD negative, but then you start to see them relapse quickly,” she said. “By 1 year, we’re starting to see a sizable amount, and then at almost a 2-year follow-up, [approximately] 60% of them are still in remission or have not undergone progression.”

Findings from MASTER and other studies show that “high-risk patients are still falling out” of remission, Callander added. “This is the area where we’re going to probably be incorporating different agents with different mechanisms,” she said.

Another quadruplet regimen incorporating isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) is being tested in the phase 2 GMMG-CONCEPT trial (NCT03104842) in patients newly diagnosed with high-risk MM. Isa-KRd was administered as induction and consolidation therapy with high-dose melphalan for patients eligible for transplant. High risk is defined as the presence of del(17p), t(4;14), t(14;16), or more than 3 copies of 1q21 in combination with stage II or stage III disease.

Investigators reported findings for 99 participants treated with Isa-KRd who were eligible for transplant and 26 who received the quadruplet but were not transplant candidates during the American Society of Hematology Annual Meeting and Exposition in December 2022.

Patients in both the transplant and nontransplant arms experienced a significant benefit in terms of MRD negativity (

 = .012, respectively). The overall response rate (ORR) among transplant-eligible patients was 94.9%, with a 72.7% rate of complete remission (CR) or better and an 18.2% very good partial response rate. Meanwhile, 57.7% of patients who did not undergo transplant displayed a CR or better and 30.8% had a very good partial response.

“We’ve been early adopters of anti-CD38 monoclonal antibody–based therapy and up-front therapy both for transplant-eligible and -ineligible patients,” Bal said. “Routinely, we are incorporating a monoclonal antibody in our transplant-eligible patients and using it in a quadruplet setting, mostly because the benefit that high-risk patients achieve is certainly worthwhile.”

Bal said that although transplant plays an important role in high-risk patients, those with standard-risk disease also benefit greatly. It is therefore reasonable to offer the option to all eligible patients, she said.

Another option for transplant-ineligible patients with newly diagnosed disease is the combination of daratumumab plus lenalidomide and dexamethasone (D-Rd). This triplet was compared with Rd alone in the phase 3 MAIA trial (NCT02252172).

At a median follow-up of 64.5 months, patients who received D-Rd (n = 368) had a median PFS of 61.9 months vs 34.9 months for participants who received RD (n = 369), which translated into an HR of 0.55 (95% CI, 0.450.67; 

 < .0001), according to updated findings presented at the ASH meeting. D-Rd therapy also improved OS, with an HR of 0.66 (95% CI, 0.53-0.83; P = .0003).

Additionally, the estimated 60-month OS rates with D-Rd and RD were 66.6% vs 53.6%, respectively, and the ORRs were 92.9% vs 81.6%, respectively (

 < .0001). The MRD negativity rates were 32.1% vs 11.1%, respectively (

The MAIA findings provide evidence of a safe, effective regimen that is easy to administer for patients who are truly not eligible for transplant, Garfall said. He and other panelists noted that therapy could be tailored to the needs of the individual patient with the addition of a PI.

Bispecific antibodies are emerging as an important innovation in MM and other malignancies, Garfall noted. These novel agents join CAR therapies as options that are being introduced in the relapsed/refractory setting.

In October 2022, teclistamab-cqyv (Tecvayli) became the first bispecific antibody to gain FDA approval in MM.

 Teclistamab is a T-cellengaging antibody that binds to the CD3 receptor on the surface of T cells and B-cell maturation antigen (BCMA) expressed on the surface of MM cells, as well as some healthy B lineage cells.

 It is approved for the treatment of adults with relapsed/refractory MM following at least 4 previous lines of treatment including a PI, an IMiD, and an anti-CD38 antibody.

The approval of teclistamab was supported by findings from the phase 1/2 MajesTEC-1 trial (NCT03145181; NCT04557098). Single-agent therapy demonstrated an ORR of 61.8% (95% CI, 52.1%-70.9%), with an estimated duration of response (DOR) rate of 66.5% (95% CI, 38.8%-83.9%) at 9 months.

Updated findings from the study with extended follow-up were presented during ASCO 2023. At a median follow-up of 22 months, patients who received the recommended phase 2 dose of teclistamab (n = 165) achieved a median DOR of 24 months (95% CI, 16.2-NE), a median PFS of 12.5 months (95% CI, 8.8-17.2), and a median OS of 21.9 months (95% CI, 16.0-NE). Notably, 43% of patients achieved at least a CR, and the median DOR among those who experienced a CR was not yet reached (95% CI, 24.0-NE).

 program, the panelists discussed a case study of a 74-year-old woman with IgAλ MM who was treated with teclistamab after undergoing 4 prior lines of therapy, including 2 PIs, 2 IMiDs, and a monoclonal antibody. She achieved a stringent CR (sCR), but had difficulty battling upper respiratory infection symptoms and COVID-19.

Garfall, who is among the key investigators in MajesTEC-1, said that teclistamab’s efficacy was “remarkable” for a patient refractory to prior therapies, but that the patient faced complications.

“Without teclistamab, we would be thinking about salvage stem cell transplant for this patient in her mid-70s or recycling prior agents, with a real risk of complications and progressive disease,” he said. “She’s been in a complete response now for years. But nonetheless, she did not handle otherwise routine infections well. [She] ended up getting a subsequent superinfection. So the myeloma is under tremendous control, but she’s had some complications.”

Besides teclistamab, several other bispecific antibodies have reached the later stages of clinical development. These include elranatamab (PF-06863135), talquetamab (JNJ-64407564), and linvoseltamab (REGN5458; 

The FDA has granted a priority review for a biologics license application (BLA) for elranatamab, which targets BCMA and CD3, for patients with relapsed/refractory MM; a decision is expected in 2023.

 A BLA for an indication in a similar setting is pending for talquetamab, a bispecific T-cell engager that targets GPRC5D and CD3.

 Meanwhile, a regulatory filing is planned in 2023 for linvoseltamab, which also is directed at BCMA and CD3.

Updated findings from pivotal trials involving these agents were presented during the 2023 ASCO meeting. In each study, the bispecifics were administered as monotherapy to patients who had undergone at least 3 prior lines of therapy.

In the phase 2 MagnetisMM-3 trial (NCT04649359), patients who received elranatamab (n = 123) exhibited an ORR of 61.0% (95% CI, 51.8%-69.6%), including 35.0% with a CR or sCR after a median follow-up of 14.7 months. The median DOR had not yet been reached and the estimated 15-month DOR rate was 71.5% (95% CI, 58.8%-80.9%).

In the phase 2 MonumenTAL-1 study (NCT03399799; NCT04634552),patients who received talquetamab achieved ORRs of 74.1% and 71.7% when treated on a dosing schedule of weekly (n = 143) and once every 2 weeks (n = 145) therapy, respectively. The median DORs were 9.5 months (95% CI, 6.7-13.3) and not reached (95% CI, 13.0-NE), respectively.

In the phase 2 LINKER-MM1 trial (NCT03761108), patients who received the agent at the recommended 200-mg dose (n = 117) achieved an ORR of 71%, including a CR rate of 14% and an sCR rate of 16%, at a median follow-up of 5.6 months. The median PFS for patients who received this dose had not yet been reached.

Many questions about the use of bispecifics in clinical practice remain unanswered, the 

 panelists indicated. “We’re going to have to see whether there are some real differences that emerge [between these agents]—probably not so much in terms of response rate, but more administration time and possibly cytokine release syndrome differences,” Callander said. “The biggest issue is going to be the sequencing. Let’s say this patient walks in the door and you have the option to do a bispecific or a CAR T-cell [therapy]. What are you going to do first?”

Beyond bispecific antibodies, CAR T-cell therapies continue to gain a foothold in the relapsed/refractory MM treatment paradigm. There are 2 FDA-approved CAR T-cell treatments for patients with MM: idecabtagene vicleucel (ide-cel; Abecma) and ciltacabtagene autoleucel (cita-cel; Carvykti).

Ide-cel became the first FDA-approved cellbased gene therapy for MM when the agency gave it the green light for patients who had undergone 4 or more lines of therapy in March 2021.

In February 2022, the FDA approved cilta-cel for patients with relapsed/refractory MM following treatment with at least 4 prior lines.

Ide-cel was approved based on findings from the phase 2 KarMMa trial (NCT03361748). At the time of ide-cel’s approval, patients in the efficacy population who received the agent (n = 100) experienced an ORR of 72% (95% CI, 62%-81%), with an sCR rate of 28% (95% CI, 19%-38%).

Results from the phase 1/2 CARTITUDE-1 trial (NCT03548207) supported the approval of cilta-cel. This trial demonstrated that patients who received cilta-cel (n = 97) experienced an ORR of 97.9% (95% CI, 92.7%-99.7%) including an sCR of 78.4%.

Final results from CARTITUDE-1, presented during ASCO 2023, showed that the median PFS was 34.9 months (95% CI, 25.2-NE). The 30- and 36-month PFS rates were 54.2% and 47.5%, respectively.

 Study authors noted that “longer median PFS was observed after a single infusion of cilta-cel than any previously reported therapy in heavily pretreated patients with relapsed/ refractory [MM].”

 The phase 4 CARTINUE study (NCT05201781) will monitor patients treated with cilta-cel for new safety and survival signals for up to 15 years.

Differences in clinical trial populations make it difficult to compare response of CAR T-cell therapies with emerging bispecifics, Garfall said. “I would caution against overinterpreting those top-line response rates and think of all these together as remarkable options for patients.”

The next front in CAR T-cell therapy involves moving these agents into earlier lines of MM treatment. During ASCO 2023, investigators presented results from the phase 3 CARTITUDE-4 trial (NCT04181827) in patients with lenalidomide-refractory MM following 1 to 3 prior lines of therapy. The study compared treatment with cilta-cel vs standard of care with pomalidomide, bortezomib, and dexamethasone or daratumumab, pomalidomide, and dexamethasone.

At a median follow-up of 15.9 months, the median PFS was not reached (95% CI, 22.8-NE) in patients who received the CAR T-cell therapy (n = 208) compared with 11.8 months (95% CI, 9.7-13.8) in patients (n = 211) treated with standard-of-care therapies (HR, 0.26; 95% CI, 0.18-0.38; 

 < .0001). The 12-month PFS rates were 76% vs 49%, respectively.

Findings from CARTITUDE-4 form the basis for a supplemental BLA for the use of cilta-cel in patients with relapsed and lenalidomide- refractory MM who have received at least 1 prior therapy, including a PI and an IMiD.

Another phase 3 study, the KarMMa-3 trial (NCT03651128), is also aiming to test CAR T-cell therapy in earlier treatment lines by comparing the safety and efficacy of ide-cel with that of 5 standard-of-care regimens. The study enrolled patients with relapsed/refractory MM whose disease was refractory to the last regimen and had received 2 to 4 total previous regimens. In all, 386 participants were randomly assigned 2:1 to receive either ide-cel or a standard regimen.

At a median follow-up of 18.6 months, the median PFS in the ide-cel arm (n = 254) was 13.3 months (95% CI, 11.8-16.4) vs 4.4 months (95% CI, 3.4-5.9) in the standard regimen arm (HR, 0.49; 95% CI, 0.38-0.65; 

 < .001). Moreover, the ORRs were 71% (95% CI, 66%-77%) vs 42% (95% CI, 33%-50%), respectively (OR, 3.47; 95% CI, 2.245.39; 

 < .001), with respective rates of CR or sCR of 39% vs 5%. The safety profile of the CAR T-cell agent was found to be consistent with what had been previously reported.

Interim findings from KarMMa-3 support a supplemental BLA that the FDA is reviewing for ide-cel in patients with MM who have relapsed after therapy with an IMiD, a PI, and an anti-CD38 monoclonal antibody. The agency is scheduled to decide on the application by December 16, 2023.

“There [was some] disappointment that the PFS wasn’t better [in KarMMa-3],” Callander, who participated in the study, said. However, she noted that participants were highly refractory. “Most of them were triple refractory. They had a high incidence of high-risk cytogenetics, so it’s not an accident that the control group did as [poorly] as they did. That sort of indicates where [this population] is. [These results] may give us a very big signal about whether we want to move CAR T[-cell therapies] up as soon as possible.”

Garfall agreed that earlier use of CAR T-cell therapy should be considered for both logistical as well as therapeutic reasons in light of the difficulties inherent in arranging the treatments for heavily relapsed patients. “Even if [CAR T-cell agents] have similar efficacy in the intermediate-relapse setting, there’s still a great case to move them up from a feasibility perspective, because those patients do have a little more time to wait in the 1 to 3 prior lines of therapy ranges compared with [those in] the 4-plus prior lines of therapy range.”

Daratumumab injection. FDA. Updated November 16, 2015. Accessed June 24, 2023. http://wayback.archive-it.org/7993/20170111231618/http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm472904.htm 

Plasma cell neoplasms (including multiple myeloma) treatment (PDQ)–health professional version. National Cancer Institute. Updated April 14, 2023. Accessed June 21, 2023. https://www.cancer.gov/types/myeloma/hp/myeloma-treatment-pdq#_675_toc 

Richardson PG, Jacobus SJ, Weller EA, et al; DETERMINATION Investigators. Triplet therapy, transplantation, and maintenance until progression in myeloma. 

Leading investigators in the multiple myeloma field discuss the latest clinical trial findings, many of which were presented during the 2023 ASCO Annual Meeting. 

Vol. 24/No. 12 | Oncology Live®

Updates on Imaging-Based Pancreatic Cancer Surveillance for Individuals With Increased Genetic and Familial Risk

PROSPECT Trial Looks to Add Effective Option for Patients With R/R PCNSL

Explorations Unearth New Potential of KRAS Mutations in Pancreatic Cancer

Novel Agents Highlight Changes in Myeloma Field

Interpreting Clinical Trial Data Is Not as Simple as It May Seem