Dr Feldman on the Importance of the TRANSCEND CLL 004 Trial in CLL/SLL

Tatyana Feldman, MD, hematologist, director, T Cell Lymphoma Program, John Theurer Cancer Center, Hackensack University Medical Center, discusses the importance of the phase 1/2 TRANSCEND CLL 004 trial (NCT03331198) investigating lisocabtagene maraleucel (liso-cel; Breyanzi) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

This trial holds significant importance due to the evolution of CLL treatment, Feldman begins. Although oncologists have witnessed remarkable advancements with treatment options such as BTK inhibitors and BCL-2 inhibitors, drastically altering the prognosis for patients with CLL, there has been a notable emergence of relapses among patients after long-term or even short-term treatment with these inhibitors, Feldman explains. Despite ongoing studies exploring various treatment avenues, one particularly noteworthy study is the TRANSCEND CLL 004 trial, she elucidates.

After the primary analysis findings from TRANSCEND CLL 004 were presented, at the 

, a 24-month median follow-up analysis was presented, Feldman says. The trial focused on adult patients with relapsed/refractory CLL, including a cohort of double-refractory patients who had progressed on both BTK inhibitor– and venetoclax (Venclexta)–based treatments, she reports. This population presents a considerable treatment challenge due to their notably short overall survival outcomes, Feldman adds.

Patients in the trial received liso-cel at 2 dose levels, with the second dose level being the standard for all patients, Feldman continues. The study comprised 2 cohorts: 1 encompassing all patients and another specific to venetoclax- and BTK inhibitor–pretreated patients, she concludes.

Results from the initial analysis of this research were previously disclosed, showing rapid and deep responses with the treatment. These findings played a role in the FDA's 

review of the supplemental biologics license application

 for liso-cel for patients with relapsed/refractory CLL or SLL. This application sought to broaden the approved use of liso-cel to encompass patients diagnosed with CLL and SLL who had previously received treatment with both a BTK inhibitor and a BCL-2 inhibitor.

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Tatyana Feldman, MD, discusses the TRANSCEND CLL 004 trial in patients with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma.

Tatyana Feldman, MD, discusses the launch of the TRANSCEND CLL 004 trial in relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma.

Dr Feldman on the Background of the TRANSCEND CLL 004 Trial in CLL/SLL

Tatyana Feldman, MD, hematologist, director, T Cell Lymphoma Program, John Theurer Cancer Center, Hackensack University Medical Center, discusses the rationale for launching the phase 1/2 TRANSCEND CLL 004 trial (NCT03331198) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), highlighting some of the methodologies that were used in the investigation.

The multicenter, single-arm study explored the effectiveness of lisocabtagene maraleucel (Breyanzi; liso-cel), a CAR T-cell therapy, in patients diagnosed with CLL/SLL who had experienced disease progression after treatment with both a BTK inhibitor and a venetoclax (Venclexta)–based regimen. Results from the initial analysis of this trial were previously reported, revealing notable responses to the treatment, as assessed at a median follow-up of 21.1 months (range 0.4-55.6). These 

prompted the FDA to grant priority review

a supplemental biologics license application

 aimed at expanding the indication of liso-cel to encompass patients with CLL and SLL who had previously received treatment with both a BTK inhibitor and a BCL-2 inhibitor.

The significance of this trial cannot be overstated, particularly in the context of the vast array of treatment options for patients with CLL, Feldman begins. These treatment options, such as BTK inhibitors and BCL-2 inhibitors, have significantly improved outcomes for patients with CLL, leading to prolonged survival and a decrease in the exhaustion of treatment options, she states. However, investigators have reached a juncture where they are witnessing relapses in patients who have received prolonged treatment, including those with extended exposure to BTK inhibitors or BCL-2 inhibitors, Feldman explains. Despite the availability of various treatment options, one of the pivotal studies shedding light on this issue is the TRANSCEND CLL 004 study, she elucidates.

Investigators reported the 24-month median follow-up analysis of TRANSCEND CLL 004 at the 

, she continues. The trial enrolled adult patients with relapsed/refractory CLL, including those who had progressed on both BTK inhibitor– and venetoclax-based treatments. Patients received liso-cel at 2 dose levels, with the second dose level deemed appropriate for all patients. The study encompassed 2 cohorts: one comprising all patients and another specific to those previously treated with venetoclax and BTK inhibitors, she concludes.

Dr Feldman on Updated Findings From the TRANSCEND CLL 004 Trial in CLL/SLL

Tatyana Feldman, MD, hematologist, director, T Cell Lymphoma Program, John Theurer Cancer Center, Hackensack University Medical Center, discusses updated safety and efficacy data from the phase 1/2 TRANSCEND CLL 004 trial (NCT03331198) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

The single-arm, multicenter study investigated the efficacy of the CAR T-cell therapy lisocabtagene maraleucel (Breyanzi; liso-cel) in patients with CLL/SLL who experienced disease progression on both a BTK inhibitor and a venetoclax (Venclexta)–based regimen.

Findings from the primary analysis of this study were previously reported and demonstrated rapid and deep responses with the agent at a median follow-up of 21.1 months (range 0.4-55.6). These data supported the FDA's decision to grant 

priority review to the supplemental biologics license

 to include patients with CLL and SLL who had prior exposure to a BTK inhibitor and a BCL2 inhibitor.

A longer median follow-up analysis was conducted in the primary efficacy analysis set, Feldman begins. This population featured a subset of patients who had experienced disease progression following treatment with a BTK inhibitor and BCL2 inhibitor and received liso-cel at a target dose of 100 x 106 CAR+ T cells. At a median follow-up of 23.5 months (range, 0.4-59.6), patients experienced a complete response rate of 20% (95% CI, 10.0%-33.7%) with liso-cel, Feldman reports.

Additionally, the agent elicited sustained undetectable minimal residual disease rates in both blood (64%; 95% CI,45.2%-77.1%) and bone marrow (60%; 95% CI,45.2%-73.6%), she states. The overall response rate with the agent was 44% (95% CI, 30.0%-58.7%), and the median duration of response was 35.3 months (range, 11.01-not reached), Feldman adds. A signal for overall survival benefit was also observed, although further data are needed to confirm this finding, Feldman notes.

Regarding safety, the study reported manageable adverse effects with liso-cel, Feldman continues. There was an 85% incidence of any-grade cytokine release syndrome (CRS) and a 45% incidence of non-CRS neurological events. Importantly, most of these events were low grade, indicating the agent’s favorable safety profile, she says.

Overall, results show that liso-cel may serve as a valuable addition to the treatment armamentarium for this patient subset, and investigators anticipate the agent's expanded approval in both CLL and SLL, Feldman concludes.

Tatyana Feldman, MD, discusses updated safety and efficacy data from the phase 1/2 TRANSCEND CLL 004 trial in patients with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma.

Dr Feldman on Updated Findings From the TRANSCEND CLL 004 Trial in CLL/SLL  

Tatyana Feldman, MD, hematologist and medical oncologist, John Theurer Cancer Center, discusses the efficacy of adding etoposide to brentuximab vedotin (Adcetris) plus CHP (cyclophosphamide, doxorubicin, and prednisone) followed by brentuximab vedotin consolidation in patients with newly diagnosed, CD30-expressing peripheral T-cell lymphomas (PTCL).

Data from the multicenter, phase 2 trial (NCT03113500) were presented at the 

, which evaluated the safety and efficacy of the regimen in this patient population. Results showed that the 18-month progression-free survival (PFS) rate was 61% with this approach for all patients. The 18-month PFS rate was 81% in patients with anaplastic large cell lymphoma (ALCL), according to Feldman. The majority of patients with ALCL were 

 positive, Feldman says. Notably, the 18-month PFS rate was 49% in patients with non-ALCL PTCLs, Feldman adds.

Additionally, patients with ALCL achieved an overall response rate (ORR) of 94% with this approach, and all responses were complete responses (CRs), Feldman notes. Patients with PTCL NOS experienced the worst responses with this regimen; the ORR was 82% and the CR rate was 55% in this population, Feldman reports. In patients with angioimmunoblastic T-cell lymphoma, the regimen induced an ORR of 94% with a CR rate of 82%, Feldman concludes. 

Tatyana Feldman, discusses the efficacy of adding etoposide to brentuximab vedotin followed by brentuximab vedotin consolidation in patients with newly diagnosed, CD30-expressing peripheral T-cell lymphomas.

Dr. Feldman on Adding Etoposide to Brentuximab Vedotin/CHP in Peripheral T-Cell Lymphomas 

Tatyana Feldman, MD, hematologist and medical oncologist, John Theurer Cancer Center, discusses the utility of PET scan in Hodgkin Lymphoma.

 Patients with Hodgkin lymphoma may develop residual masses in the mediastinum, making it difficult to differentiate active disease from scar tissue with a CAT scan, says Feldman. 

As such, patients were historically overtreated and radiation was commonly used, explains Feldman. Additionally, splenic disease was not often detected with CAT scan. 

PET scan was a major advancement in this field, says Feldman. Moreover, the majority of patients who have negative PET scan results after 2 cycles of chemotherapy are considered cured. 

Multiple randomized phase III trials have demonstrated the utility of PET scan, says Feldman. Patients with bulky disease or early-stage disease may be spared radiation therapy or receive deescalated chemotherapy based on PET scan results. 

As there are some limitations to PET scan, circulating tumor DNA testing may provide an alternative modality to accurately evaluate complete responses versus progressive disease in patients with Hodgkin lymphoma.

Tatyana Feldman, MD, discusses the utility of PET Scan in Hodgkin Lymphoma.

Dr. Feldman on the Utility of PET Scan in Hodgkin Lymphoma

Tatyana Feldman, MD, hematologist and medical oncologist, John Theurer Cancer Center, discusses the shortcomings of PET scan in Hodgkin lymphoma.

About 80% of patients who have negative PET scan results after 2 cycles of doxorubicin, vinblastine, dacarbazine, and bleomycin (ABVD; PET2) are considered cured regardless of whether there is residual disease, says Feldman. However, a PET scan cannot identify the PET2-negative patients who will relapse, adds Feldman.

Additionally, combination approaches need to be fleshed out to determine which individuals are best suited for which regimen. For example, certain patients with positive scans may not require further treatment, says Feldman. However, certain patients with positive scans may need additional treatment, and there is no way to tell which category a patient will fall into with a PET scan. Novel agents may place a role for patients who need additional therapy. Further research may shed light on ways to avoid overtreatment as well as optimal treatment strategies for patients with residual disease.

Tatyana Feldman, MD, discusses the shortcomings of PET scan in Hodgkin lymphoma.

Dr. Feldman on the Shortcomings of PET Scan in Hodgkin Lymphoma

Tatyana Feldman, MD, a hematologist and oncologist specializing in lymphoma at the John Theurer Cancer Center at Hackensack University Medical Center, discusses the phase II multicenter trial examining the introduction of pegylated liposomal doxorubicin (PLD) followed by bexarotene for patients with advanced cutaneous T-cell lymphoma (CTCL).

Patients with advanced or refractory CTCL received 8 doses of PLD every 2 weeks. After the 16-week process response rate was gathered to gauge the efficacy of single agent PLD. If the patients responded they would receive an additional 16 weeks of oral bexarotene, an antineoplastic agent that is an retinoic acid receptor antagonist, which has demonstrated a 50% overall response rate (ORR) in relapsed or refractory CTCL.

Once treatment is stopped for patients with CTCL the disease generally recurs. The goal of the trial was to prolong the effects of bexarotene in order to extend progression-free survival (PFS). The median PFS in the trial was 4.82 months with an ORR of 41%.

Dr. Tatyana Feldman, from the John Theurer Cancer Center, Discusses Using Doxil for CTCL

Dr. Feldman Discusses Using Doxil for CTCL

Tatyana Feldman, MD, a hematologist and oncologist who specializes in lymphoma at John Theurer Cancer Center at Hackensack University Medical Center in Hackensack, NJ, discusses how difficult it is to treat rare forms of lymphoma. Many of these cases are diagnosed in early stages and pose more of a nuisance to the patient, but later stages are very serious, and there are not as many good therapies that exist for treating this relatively small population of patients.

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Dr. Tatyana Feldman from John Theurer Cancer Center Discusses the Difficulties of Rare Lymphomas

Tatyana Feldman, MD

Articles

Dr Feldman on the Importance of the TRANSCEND CLL 004 Trial in CLL/SLL

Dr Feldman on the Background of the TRANSCEND CLL 004 Trial in CLL/SLL

Dr Feldman on Updated Findings From the TRANSCEND CLL 004 Trial in CLL/SLL

Dr. Feldman on Adding Etoposide to Brentuximab Vedotin/CHP in Peripheral T-Cell Lymphomas

Dr. Feldman on the Utility of PET Scan in Hodgkin Lymphoma

Dr. Feldman on the Shortcomings of PET Scan in Hodgkin Lymphoma

Dr. Feldman Discusses Using Doxil for CTCL

Dr. Feldman Discusses the Difficulties of Rare Lymphomas