Tafasitamab Combo Meets PFS End Point in R/R Follicular Lymphoma

In the international, double-blind inMIND study (NCT04680052), 654 adult patients were assigned to receive tafasitamab or matched placebo in combination with lenalidomide and rituximab.The study population consisted of patients with relapsed/refractory grade 1 to 3a follicular lymphoma or refractory nodal, splenic, or extranodal marginal zone lymphoma.

Combining tafasitamab-cxix (Monjuvi) with lenalidomide (Revlimid) and rituximab (Rituxan) met the primary end point of progression-free survival (PFS) per investigator assessment in patients with relapsed/refractory follicular lymphoma, according to a press release on topline data from the phase 3 inMIND trial (NCT04680052).¹

Findings also showed that tafasitamab-based treatment met the secondary end points of PFS in the overall trial population and PET complete response (CR) rate among patients with FDG-avid follicular lymphoma. Additionally, PFS outcomes based on blinded independent central review aligned with investigator assessment. Treatment with tafasitamab yielded no new safety signals.

Developers intend to submit a supplemental biologics license application (sBLA) for tafasitamab as a treatment for follicular lymphoma following progression on systemic anti-CD20 or chemoimmunotherapy agents based on data from the inMIND trial. This submission is anticipated by the end of 2024. Investigators also plan to submit full findings from the inMIND trial for presentation at a future scientific meeting.

“[Although] many patients with follicular lymphoma initially benefit from first-line treatment, relapse of the disease is common, underscoring the need for additional therapies. These results demonstrate the potential of tafasitamab added to the standard of care to be a meaningful new treatment option for patients with [follicular lymphoma] whose disease has progressed after at least 1 prior therapy,” Steven Stein, MD, chief medical officer at Incyte, the developer of tafasitamab, said in the press release.¹

Tafasitamab, a humanized Fc-modified cytolytic anti-CD19 monoclonal antibody, makes use of the XmAb® engineered Fc domain to facilitate B-cell lysis via apoptosis and antibody-dependent cell-mediated cytotoxicity and antibody-dependent cellular phagocytosis.

In the international, double-blind inMIND study, 654 adult patients were assigned to receive tafasitamab or matched placebo in combination with lenalidomide and rituximab. The study population consisted of patients with relapsed/refractory grade 1 to 3a follicular lymphoma or refractory nodal, splenic, or extranodal marginal zone lymphoma (MZL).

The trial’s secondary end points included minimal residual disease (MRD)–negative status in the follicular lymphoma and MZL populations, overall survival, CR rate, duration of response, quality of life, and safety.²

Patients 18 years and older with histologically confirmed grade 1, 2, or 3a follicular lymphoma; nodal MZL; splenic MZL; or extra nodal MZL were eligible for enrollment on the trial. Additional eligibility criteria included having willingness to undergo mandatory prophylaxis and/or therapy for thromboembolic events, prior treatment with 1 or more lines of anti-CD20 immunotherapy or chemoimmunotherapy, and an ECOG performance status of 0 to 2. Having documented relapsed, refractory, or progressive disease following prior systemic therapy was another requirement for study entry.

Those with any disease histology apart from follicular lymphoma and MZL or evidence of transformed lymphoma were unable to enroll on the trial. Patients were also unsuitable for enrollment if they had a prior non-hematologic malignancy, congestive heart failure, an active systemic infection, central nervous system (CNS) lymphoma involvement, or prior treatment with lenalidomide plus rituximab.

The FDA previously granted accelerated approval to tafasitamab plus lenalidomide for adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified in July 2020.³ As part of the approval, the combination was also indicated for use in patients with DLBCL arising from low-grade lymphoma and those not eligible to undergo autologous stem cell transplant.

Supporting data for the accelerated approval came from the phase 2 L-MIND trial (NCT02399085). The best objective response rate among 71 evaluable patients with centrally confirmed DLBCL was 55% (95% CI, 43%-67%) following treatment with tafasitamab/lenalidomide, which included CRs in 37% and partial responses in 18%.

References

1. Incyte announces positive topline results from pivotal study of tafasitamab (Monjuvi®) in relapsed or refractory follicular lymphoma. News release. Incyte. August 15, 2024. Accessed August 16, 2024. https://tinyurl.com/49h4edk6
2. A phase 3 study to assess efficacy and safety of tafasitamab plus lenalidomide and rituximab compared to placebo plus lenalidomide and rituximab in patients with relapsed/​refractory (R/​R) follicular lymphoma or marginal zone lymphoma. (InMIND). ClinicalTrials.gov. Accessed August 14, 2024. https://tinyurl.com/3zk3y3y7
3. FDA grants accelerated approval to tafasitamab-cxix for diffuse large B-cell lymphoma. News release. FDA. July 31, 2020. Accessed August 16, 2024. https://tinyurl.com/yc3eh5wz