Matthew J. Matasar, MD, medical oncologist, director, Regional Care Network Medical Site, Memorial Sloan Kettering Cancer Center, discusses the unmet needs remaining in diffuse large B-cell lymphoma (DLBCL).

Though investigators and clinicians have made significant strides in treating patients with relapsed/refractory DLBCL, significant toxicities have affected the risk/benefit profile for using these agents, Matasar says. Developing more effective and better tolerated immunotherapy options remains an unmet need in DLBCL, particularly because the disease typically affects older patients with comorbidities, Matasar adds.

The phase 2b VITALIZE trial (NCT04920617) investigated maveropepimut-S plus pembrolizumab (Keytruda) and low dose, intermittent cyclophosphamide in relapsed/refractory DLBCL. Maveropepimut-S targets survivin, which is a cancer-associated protein commonly upregulated in advanced DLBCL.

Developing an immunotherapeutic strategy to target survivin could represent a novel way to leverage immunotherapy for patients with relapsed or refractory DLBCL, Matasar concludes.

Videos

Matthew J. Matasar, MD, discusses the unmet needs remaining in diffuse large B-cell lymphoma.


Dr. Matasar on the Unmet Needs of Immunotherapy for DLBCL

Matthew J. Matasar, MD, a medical oncologist, and Regional Care Network Medical Site Director at Memorial Sloan Kettering Cancer Center Bergen, discusses the rationale for combining copanlisib (Aliqopa) and rituximab (Rituxan) in patients with indolent non-Hodgkin lymphoma (iNHL). 

For patients with relapsed indolent B-cell lymphomas, particularly those who have been sensitive to rituximab and have experienced long durations of remission following treatment, single-agent rituximab continues to be a standard option, according to Matasar. However, response rates to rituximab alone tend be lower, with a less-than-desirable duration of response, Matasar adds. Due to this, research efforts are focused on developing more effective, less toxic therapies to offer this patient population, Matasar explains.

Prior attempts to combine oral daily PI3K inhibitors with rituximab have been hindered by excessive adverse effects such as pneumonitis, enteritis, and hepatitis. The phase 3 CHRONOS-3 trial (NCT02367040) sought to overcome these prior challenges by adding copanlisib, an intravenously and intermediately administered PI3K inhibitor, to the agent, Matasar concludes.

Matthew J. Matasar, MD, Memorial Sloan Kettering Cancer Center Bergen, discusses the rationale for combining copanlisib and rituximab in patients with indolent non-Hodgkin lymphoma. 

Dr. Matasar on the Rationale for Combining Copanlisib and Rituximab in Indolent NHL

Matthew J. Matasar, MD, a medical oncologist and Regional Care Network Medical Site Director at Memorial Sloan Kettering Cancer Center Bergen, discusses the design of the phase 3 CHRONOS-3 trial (NCT02367040) in indolent non-Hodgkin lymphoma (iNHL).

In the globally conducted, randomized CHRONOS-3 trial, patients with iNHL received either copanlisib (Aliqopa) plus rituximab (Rituxan) or rituximab plus placebo, Matasar says. Patients were randomized 2:1, meaning that of every 3 patients who enrolled to the trial, 2 patients would receive the combination regimen, while 1 would receive rituximab plus a placebo. A total of 458 patients were randomized; of these patients, 307 received the copanlisib combination and 151 received rituximab plus placebo, Matasar concludes.

Matthew J. Matasar, MD, discusses the design of the phase 3 CHRONOS-3 trial in indolent non-Hodgkin lymphoma.

Dr. Matasar on the Design of the CHRONOS-3 Trial Examining Copanlisib/Rituximab in Indolent NHL

Matthew J. Matasar, MD, a medical oncologist and Regional Care Network Medical Site Director at Memorial Sloan Kettering Cancer Center Bergen, discusses the efficacy of copanlisib (Aliqopa) plus rituximab (Rituxan) in patients with relapsed indolent non-Hodgkin lymphoma (iNHL).

In the phase 3 CHRONOS-3 trial (NCT02367040), the combination was compared with placebo plus rituximab. The primary end point of the trial was to identify an improvement in progression-free survival (PFS), which was met, according to Matasar. After pooling data from the indolent B-cell histologies that were included in the study, investigators observed a net improvement in median PFS, going from 13.8 months with rituximab plus placebo to 21.5 months with copanlisib plus rituximab; this finding was statistically and clinically significant, Matasar says. 

Additionally, benefit was observed across the different histologic subtypes examined, including follicular lymphoma, marginal zone lymphoma, and small lymphocytic lymphoma. A numerical improvement was also observed in patients with Waldenström macroglobulinemia and lymphoplasmacytic lymphoma; however, this did not achieve statistical significance, possibly due to the small number of patients in this subgroup. Improvements in the overall response rate and complete response rate were also reported with the combination, in the pooled histologies and individual histologies, Matasar concludes.

Matthew J. Matasar, MD, discusses the efficacy of copanlisib plus rituximab in patients with relapsed indolent non-Hodgkin lymphoma.



Dr. Matasar on the Efficacy of Copanlisib Plus Rituximab in Indolent NHL

Matthew J. Matasar, MD, attending physician, Memorial Sloan Kettering Cancer Center, discusses antibody drug conjugates (ADCs) in B-cell malignancies.

Polatuzumab vedotin, an ADC, is being studied in combination with rituximab (Rituxan) or obinutuzumab (Gazyva) in patients with relapsed/refractory follicular lymphoma or diffuse large B-cell lymphoma (DLBCL).

As for ADCs in this space, there has been success with brentuximab vedotin, which is approved by the FDA in classical Hodgkin lymphoma.

Matthew J. Matasar, MD, attending physician, Memorial Sloan Kettering Cancer Center, discusses antibody drug conjugates in B-cell malignancies.

Matthew J. Matasar, MD

Articles

Dr. Matasar on the Unmet Needs of Immunotherapy for DLBCL

Dr. Matasar on the Rationale for Combining Copanlisib and Rituximab in Indolent NHL

Dr. Matasar on the Design of the CHRONOS-3 Trial Examining Copanlisib/Rituximab in Indolent NHL

Dr. Matasar on the Efficacy of Copanlisib Plus Rituximab in Indolent NHL

Dr. Matasar on Antibody-Drug Conjugates in B-Cell Malignancies