Jonathan E. Brammer, MD,discusses data from the following poster: “Duvelisib in Patients With Relapsed/Refractory Peripheral T-Cell Lymphoma From the Phase 2 PRIMO Trial: Results of an Interim Analysis” 

Brammer J, et al. ASH 2021, Abstract 2456

Relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL) is a family of aggressive lymphomas, with a median overall survival (OS) of less than 6 months. Current FDA-approved therapies for R/R PTCL have modest overall response rates (ORRs) of < 30%.

In the phase 2, open-label, multicenter, parallel cohort PRIMO trial of duvelisib (a dual PI3K-δ,γ inhibitor) in R/R PTCL, the initial results of the dose-optimization phase (N=33) demonstrated a 54% ORR in the 75 mg twice a day (N=13) and 35% in the 25 mg twice a day (N=20) cohorts, respectively.

The objective of this presentation was to provide the interim results as of May 21, 2021, including the first 6 months of data for the 78 patients included in the analysis obtained from the PRIMO trial expansion phase.

PRIMO is a phase 2, open-label, multicenter, parallel cohort study of duvelisib in patients with R/R PTCL consisting of a dose optimization phase and an expansion phase (

The expansion phase of PRIMO has a targeted enrollment of 125 patients. The expansion phase eligibility criteria included histologically confirmed R/R PTCL after >1 cycle of a prior standard regimen, a CD4 lymphocyte count of ≥ 50 per mm3 and required pneumocystis jiroveci prophylaxis.

Based on the dose optimization results, patients in the expansion phase receive duvelisib at 75 mg twice a day for 2 cycles to maximize rapid tumor control, followed by 25 mg twice a day to maintain long-term disease control and mitigate late toxicities, until progressive disease or unacceptable toxicity.

The primary end point is ORR by independent review committee assessment. Secondary end points include ORR by investigator assessment, duration of response (DOR), progression-free survival, OS, disease control rate, and safety. All analyses consisted of patients who received at least 1 dose of duvelisib.

The interim results of the first 78 patients in the PRIMO expansion phase show an ORR of 50% and a CR rate of 32%.

Time to response was 53 days (range, 15 to 114 days), and median duration of response was 233 days (range, 1 to 420 days).

The most frequent grade ≥3 adverse events (AEs) were neutropenia, increased ALT/AST, rash, lymphocyte count decreased, and sepsis. Alanine aminotransferase and aspartate aminotransferase elevations were the most common AEs leading to treatment discontinuation.

Response rates with duvelisib suggest that this therapy is superior to available standard-of-care therapeutic options. These data build upon prior reports demonstrating duvelisib as an active oral treatment for patients with R/R PTCL.

Duvelisib was well tolerated in the given patient population and remained consistent with its known safety profile.

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Jonathan E. Brammer, MD, reports data presented at the 2021 American Society of Hematology Annual Meeting regarding interim analysis study results from the phase 2 PRIMO trial evaluating the use of duvelisib monotherapy in patients with relapsed/refractory peripheral T-cell lymphoma.

Rapid Readouts: Interim Analysis Results From the Phase 2 PRIMO Trial in R/R Peripheral T-Cell Lymphoma

Jonathan E. Brammer, MD, assistant professor, internal medicine, The Ohio State University Comprehensive Cancer Center—James, discusses data that have been reported with inotuzumab ozogamicin (Besponsa) in acute lymphoblastic leukemia (ALL).

Inotuzumab ozogamicin is an antibody-drug conjugate that targets CD22, which is present on B-cell ALL cells.

The phase 3 INO-VATE study showed that 80% of patients who received inotuzumab ozogamicin achieved remissions compared with 30% of those who received standard chemotherapy. However, these remissions are generally short-lived, says Brammer. It is an effective agent, but it should be considered a bridge to transplant.

In terms of adverse effects, inotuzumab ozogamicin is associated with veno-occlusive disease. In the INO-VATE trial, 14% of patients had veno-occlusive disease. Therefore, chemotherapy agents that are known to induce veno-occlusive disease, such as busulfan, should be avoided when using this drug, says Brammer.

Although blinatumomab (Blincyto) could be used as an alternative agent to avoid the potential complication of busulfan, both drugs are recommended in National Comprehensive Cancer Network guidelines as bridges to transplant, concludes Brammer.

Jonathan E. Brammer, MD, discusses data that have been reported with inotuzumab ozogamicin (Besponsa) in acute lymphoblastic leukemia (ALL).

Dr. Brammer on Data With Inotuzumab Ozogamicin in ALL

Jonathan E. Brammer, MD, assistant professor, internal medicine, The Ohio State University Comprehensive Cancer Center—–James, discusses the role of stem cell transplant in acute lymphoblastic leukemia (ALL).

Historically, the utility of allogeneic stem cell transplant (ASCT) in ALL was debated because its impact on survival was unknown, explains Brammer.

However, a study led by Nathalie Dhédin, MD, which evaluated two prospective clinical trials—–(NCT00222027) and (NCT00327678)––demonstrated a survival benefit with ASCT in patients who do not achieve minimal residual disease (MRD) negativity following treatment. Notably, the benefit was reported regardless of ALL subtype, says Brammer.

Patients who are MRD negative after chemotherapy and who do not have a high-risk subtype of ALL may not need transplant, says Brammer. However, patients should be counseled on an individualized basis to determine the optimal treatment strategy.

Notably, stem cell transplant has become safer and more effective for older patients with ALL. Historically, only patients ≤60 years old were considered transplant eligible. With reduced intensity conditioning, patients up to 75 years old may be eligible for transplant, says Brammer.

Finally, improved techniques have made it possible to use mismatched donors for some patients, concludes Brammer.

Jonathan E. Brammer, MD, discusses the role of stem cell transplant in acute lymphoblastic leukemia.

Dr. Brammer on the Role of Stem Cell Transplant in ALL

Jonathan E. Brammer, MD, assistant professor, internal medicine, The Ohio State University Comprehensive Cancer Center—–James, discusses the progression of transplant in acute lymphoblastic leukemia (ALL).

Traditionally, stem cell transplant (SCT) was indicated for patients with Philadelphia chromosome—positive disease or who failed to attain a remission; however, over time the patient populations eligible for SCT has changed as more differentiated subtypes and high-risk groups were identified, explains Brammer. Additionally, more effective therapies have emerged, making SCT less necessary.

Patients with minimal residual disease—positive disease after induction or at the end of treatment appear to derive more benefit from transplant, whether or not they receive salvage therapy, says Brammer. Without SCT, those patients will likely relapse. SCT should also be considered in patients with high-risk ALL, including early T-cell precursor ALL, mixed-lineage ALL, and Philadelphia-like ALL, concludes Brammer.

Jonathan E. Brammer, MD, discusses the progression of transplant in acute lymphoblastic leukemia.

Dr. Brammer on the Transformation of Stem Cell Transplant in ALL

Jonathan E. Brammer, MD, assistant professor, internal medicine, The Ohio State University Comprehensive Cancer Center—–James, discusses the importance of achieving minimal residual disease (MRD) negativity in relapsed/refractory acute lymphoblastic leukemia (ALL).

MRD is an important predictor of outcomes in both B-cell ALL and T-cell ALL, says Brammer. The majority of patients who are MRD positive after induction chemotherapy will relapse.

The phase II BLAST study evaluated the bispecific T-cell engager blinatumomab (Blincyto). The drug received regulatory approval in 2018 for the treatment of adult and pediatric patients with MRD-positive B-cell precursor ALL. The study confirmed that blinatumomab is effective in eradicating MRD in patients who received at least 3 cycles of prior treatment. Notably, many of these patients were subsequently eligible to receive stem cell transplantation, concludes Brammer.

Jonathan E. Brammer, MD, discusses the importance of achieving minimal residual disease negativity in relapsed/refractory acute lymphoblastic leukemia.

Dr. Brammer on the Importance of MRD in Relapsed/Refractory ALL

Jonathan E. Brammer, MD, assistant professor of hematology, Ohio State University Comprehensive Cancer Center, discusses updates in the treatment landscape of T-cell lymphoma.

T-cell lymphoma has been an area of limited progress and poor prognosis, according to Brammer. An exciting development is with brentuximab vedotin (Adcetris), which is now being utilized for patients with relapsed CD30-positive anaplastic large-cell lymphoma. Some of those patients have long-term durable remissions.

For patients with cutaneous T-cell lymphoma, brentuximab vedotin is also highly effective, adds Brammer.

Dr. Brammer on Updates in the Treatment Landscape for T-Cell Lymphoma

Jonathan E. Brammer, MD, assistant professor of hematology, Ohio State University Comprehensive Cancer Center, discusses brentuximab vedotin (Adcetris) for patients with T-cell lymphoma.

An issue in the landscape that is currently being explored is whether brentuximab vedotin is effective in the frontline setting as has been shown in Hodgkin lymphoma. Preliminary studies have shown that brentuximab vedotin does seem to have some efficacy in other CD30-positive T-cell lymphomas.

Jonathan E. Brammer, MD

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