ASH 2022: Addition of Lenalidomide to Rituximab Therapy is Associated with Improved Survival in Relapsed/Refractory Indolent Non-Hodgkin Lymphoma

Combination therapy with rituximab (Rituxan) and lenalidomide (Revlimid) was approved for use in relapsed/refractory indolent non-Hodgkin lymphoma (iNHL) based on the results of the phase III AUGMENT study, which were published in 2019. At ASH, John Leonard, MD, an LRF SAB member and Past-Chair, presented five-year results from AUGMENT, including survival and safety updates.

The AUGMENT study included 358 patients with R/R follicular lymphoma grade 1-3a or marginal zone lymphoma who were not refractory to rituximab. Participants received weekly ritxumab with either lenalidomide or placebo for up to one year. Survival and safety outcomes were assessed every six months during follow-up. The five-year overall survival rate was 83.2% in the rituximab-lenalidomide group and 77.3% in the rituximab-placebo group.

After a median 66 months of follow-up, the median duration of progression-free survival was 27.6 months in the lenalidomide group compared with 14.3 months in the control group. Time to next anti-lymphoma therapy was approximately 73.1 months vs 31.8 months in the lenalidomide and placebo groups, respectively.

Investigators noted that the updated safety profile was similar to what was previously reported, though additional second primary malignances (SPMs) had occurred; a total of 13 (7%) and 21 (12%) SPMs were reported in the lenalidomide and placebo groups, respectively. The overall incidence of SPMs was lower in patients who received rituximab-lenalidomide compared with those who received rituximab-placebo.

The investigators concluded that the superior efficacy and more favorable safety profile compared with rituximab monotherapy support the use of rituximab-lenalidomide therapy as a standard of care for patients with relapsed/refractory iNHL.

Durable responses achieved with glofitamab therapy in relapsed/refractory large B-cell lymphoma glofitamab is an investigational T-cell-engaging bispecific monoclonal antibody that directs T cells to eliminate cancerous B cells. Investigators reported results from a pivotal phase I/II study involving the use of glofitamab in patients with relapsed/refractory large B-cell lymphoma (LBCL). The study included 214 participants with diffuse LBCL not otherwise specified, high-grade B-cell lymphoma, primary mediastinal LBCL, or transformed follicular lymphoma who had received at least one prior therapy. Patients received one week of obinutuzumab (Gazyva) pre-treatment followed by 12 cycles of glofitamab.

At the end of treatment, 29% of patients had achieved a complete response (CR). At six months following the end of treatment, CR was maintained in 74 % of these patients. At 12 months, 56% remained in complete response. Disease progression was observed in 2% of patients during this time. The median duration of CR was not reached by the time of analysis, approximately 18 months post-treatment.

The investigators concluded that relapse rates are low among patients with relapsed/refractory LCBL who achieve a complete response to glofitimab, though longer follow-up is needed to confirm the off-treatment durability of responses beyond 12 months.

This study also included contributions from Seattle Lymphoma Rounds Steering Committee member Krish Patel, MD of the Swedish Cancer Institute; LRF grantee Lorenzo Falchi, MD of Memorial Sloan Kettering Cancer Center; and past Scientific Advisory Board (SAB) member and LRF grantee Nancy Bartlett, MD of the Washington University School of Medicine.