Tafasitamab regimen confers ‘quite remarkable’ PFS benefit in advanced follicular lymphoma
Key takeaways:
- Tafasitamab-cxix plus lenalidomide and rituximab extended survival for patients with relapsed or refractory follicular lymphoma compared with placebo.
- The tafasitamab regimen also improved response.
SAN DIEGO — The addition of tafasitamab-cxix to lenalidomide and rituximab reduced risk for progression, relapse or death by more than 50% for patients with relapsed or refractory follicular lymphoma, according to study results.
Tafasitamab-cxix (Monjuvi; MorphoSys, Incyte) appeared associated with similar toxicities as placebo, findings of the randomized phase 3 inMIND trial presented at ASH Annual Meeting and Exposition showed.
“We don’t have curative therapies [for follicular lymphoma], so the goal is largely to get good response and durable benefit,” Laurie H. Sehn, MD, MPH, clinical professor at BC Cancer Centre for Lymphoid Cancer and University of British Columbia, told Healio. “The simple addition of an anti-CD19 monoclonal antibody to a well-established backbone I think really shows quite remarkable results in terms of a significant prolongation of progression-free survival. I think the study does show very clinically meaningful results.”
Background and methods
Individuals with follicular lymphoma relapse frequently and often need multiple lines of treatment, according to study background.
Chemoimmunotherapy often is used as a front-line option, but response gets shorter after multiple treatments. Immunotherapy is used in relapsed or refractory settings, but new, effective strategies are needed to improve response durability, researchers wrote.
Lenalidomide plus rituximab (Rituxan; Genentech Biogen) has been approved as a treatment option following one line of therapy.
Tafasitamab-cxix, a humanized CD19-targeted monoclonal antibody, is approved in the U.S. for use with lenalidomide for treatment of adults with relapsed or refractory diffuse large B-cell lymphoma not otherwise specified — including DLBCL arising from low-grade lymphoma — who are ineligible for autologous stem cell transplant.
In the international, double-blind inMIND trial, Sehn and colleagues evaluated the addition of tafasitamab-cxix to lenalidomide and rituximab.
The analysis included 548 adults (median age, 64 years; range, 31-88; 55% men) with relapsed or refractory CD19- and CD20-positive follicular lymphoma. All participants received at least one prior line of therapy.
Researchers randomly assigned patients to standard dosing of lenalidomide and rituximab with either IV tafasitamab-cxix (12 mg/kg on days 1, 8, 15 and 22 of cycles 1 through 3, and days 1 and 15 on cycles 4-12) or placebo. Patients received therapy for up to 12 28-day cycles.
Investigator-assessed PFS served as the primary endpoint. PET-complete response rate, OS, overall response rate, durable response, safety and time to next treatment served as secondary endpoints.
Results and next steps
At data cutoff, a higher percentage of patients assigned tafasitamab-cxix than placebo remained on treatment (19% vs. 15%).
After median follow-up of 14.1 months, results showed improved PFS by investigator assessment (median, 22.4 months vs. 13.9 months; HR = 0.43; 95% CI, 0.32-0.58) and independent review committee assessment (median, not reached vs. 16 months; HR = 0.41; 95% CI, 0.29-0.56) in the tafasitamab-cxix group.
The PFS benefit persisted across subgroups, including patients who had received multiple prior treatments, those who received previous anti-CD20 monoclonal antibodies and those who had disease progression within the prior 24 months.
“What’s most impressive is that it was very consistent in all the subgroups we looked at,” Sehn said. “The fact that [these subgroups, which are harder patients to treat] benefited similarly as the patients with lower risk, I think, is quite remarkable.”
The tafasitamab-cxix group also had improved PET-complete response rate (49.4% vs. 39.8%; OR = 1.5; 95% CI, 1.04-2.13), ORR (83.5% vs. 72.4%; OR = 2; 95% CI, 1.3-3.02), duration of response (median, 21.2 months vs. 13.6 months; HR = 0.47; 95% CI, 0.33-0.68) and time to next treatment (median, not reached vs. 28.8 months; HR = 0.45; 95% CI, 0.31-0.64).
OS analysis showed a trend toward a benefit with tafasitamab-cxix but data had not matured. Researchers plan to evaluate OS after 5 years of follow-up.
Sehn described the regimen’s safety profile as “manageable” and noted toxicities were consistent with what had been expected.
Safety analyses showed the tafasitamab-cxix and placebo groups had similar rates of treatment-emergent adverse events (99% vs. 99%), grade 3 or grade 4 adverse events (71% vs. 69.5%), serious adverse events (36% vs. 32%) and fatal adverse events (2% vs. 2%).
Rates of dose delay or interruption due to treatment-emergent adverse events (74% vs. 70%) and discontinuation (11% vs. 7%) also appeared similar between groups.
Common grade 3 or 4 grade 4 treatment-emergent adverse events included neutropenia (39.8% for tafasitamab-cxix vs. 37.5% placebo), pneumonia (8.4% vs. 5.1%), thrombocytopenia (6.2% vs. 7.4%), decreased neutrophils (5.8% vs. 6.6%), anemia (4.4% vs. 5.9%), COVID-19 (5.8% vs. 2.2%) and COVID-19 pneumonia (4.7% vs. 1.1%).
In all, the tafasitamab-cxix group had fewer deaths (5.5% vs. 8.5%) and fewer deaths due to disease progression (2% vs. 6%).
“This is the first study that has shown the value of adding an anti-CD19 monoclonal antibody to an anti-CD20,” Sehn told Healio. “It really is proof of concept. CD19 is present on the majority of B-cell lymphomas, so I think that we need more trials that are investigating this monoclonal antibody in some of the other regimens that we’re currently using.”
An important next step will be to explore evaluating the agent for treatment of other lymphoma subtypes, Sehn said.
Collapse
Sehn LH, et al. Abstract LBA-1. Presented at: ASH Annual Meeting and Exposition; Dec. 7-10, 2024; San Diego.
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