Chemotherapy-free approaches for indolent NHL and MCL

After decades of relying on chemotherapy to treat patients with lymphoma, clinical research is exploring a more targeted approach that would combine high-efficacy with minimal adverse events. This includes, small-molecule inhibitors, immune checkpoint inhibitors, antibodies, and CAR T-cells that exploit cancer-specific targets, in contrast to chemotherapy, and will kill the tumors while sparing healthy tissue.  

Recently, a number of such therapies have received approval for the treatment of lymphomas and other chemotherapy-free regimens are being explored. The topic was also discussed at several hematology meetings, including the symposium organised by the Lymphoma Hub at the International conference on malignant lymphoma (ICML) dedicated to the advancement of chemo-free approaches.

This month, through a series of articles, the Lymphoma Hub will take a closer look at chemotherapy-free treatment strategies for indolent non-Hodgkin lymphoma (iNHL) and mantle cell lymphoma (MCL). Let’s start this educational theme by recapping on some of the relevant articles and video interviews that we covered earlier this year. 

Results from the AUGMENT phase III trial: lenalidomide + rituximab for R/R MZL and FL

The phase III trial published in the Journal of Clinical Oncology investigated the efficacy of lenalidomide plus rituximab in patients with relapsed/refractory (R/R) iNHL. Superior efficacy of lenalidomide and rituximab combination was reported, compared to placebo plus rituximab in patients with R/R marginal zone lymphoma (MZL) or follicular lymphoma (FL). 

EHA 2019 | Anti-CD47 antibody, HU5F9-G4 with rituximab in R/R DLBCL and iNHL

Mark Roschewski from National Cancer Institute, Bethesda, US, reported the results of a phase Ib/II clinical trial using the first-in-class antibody HU5F9-G4 (5F9) that targets CD47, a macrophage immune checkpoint. The antibody was used in combination with rituximab to treat patients with iNHL. The combination was well tolerated and showed efficacy in R/R diffuse large B-cell lymphoma (DLBCL) and refractory FL.

Fast & furious: looking ahead to next-generation treatments & new combinations in lymphoma?

At the 2019 ASCO Annual Meeting, Maria Lia Palomba from Memorial Sloan Kettering Cancer Center, New York, US, discussed the initial results of CAR T-cell therapy for lymphoma, and the current advancements in the field. This includes more powerful cytokine-secreting CAR constructs being developed, as well as the combinations of CAR T-cells with anti-PD1 or anti-PDL1 antibodies.

ICML 2019 | Can CAR T therapy deliver long-term benefits for patients with NHL?

During ICML 2019, Sattva Neelapu from MD Anderson Cancer Center, Houston, US, talked about the potential of CAR T therapy to deliver long-term benefits to patients with NHL, including how some of the patients achieve long-term benefits with just a single infusion.

ICML 2019 | Which patients with MCL could benefit most from ibrutinib plus rituximab in the front-line setting? 

Preetesh Jain from MD Anderson Cancer Center, Houston, US, discussed the MCL patient population that would benefit the most from ibrutinib plus rituximab in the front-line setting, and how such a chemotherapy-free treatment regimen produced a response rate of almost 93% in untreated, low-risk elderly patients.

ICML 2019 | How is ME-401, a new PI3K inhibitor, different from existing PI3K inhibitors?

Andrew Zelenetz from Memorial Sloan Kettering Cancer Center, New York, US, discussed how a combination of continuous and intermittent treatment with the PI3K inhibitor ME-401 reduced toxicities and led to an overall response rate of 100% in patients with chronic lymphocytic leukemia (CLL) and 80% in patients with FL.

ICML 2019 | CLL12 study: should we treat asymptomatic, treatment-naïve patients with ibrutinib?

Petra Langerbeins from University of Cologne, Cologne, DE, talked about the CLL12 study, which reported a significant improvement in progression-free survival and event-free survival in patients with CLL, after treatment with ibrutinib.

ICML 2019 | What are the latest advances in the treatment of MCL?

Simon Rule from Plymouth University Medical School, Plymouth, UK, discussed the impact of BTK inhibitors and how they pose a challenge to conventional chemotherapy, with chemotherapy-free regimens slowly moving into front-line therapy.