Oncologists’ Guide to the FDA Approval of Tafasitamab for Relapsed FL
FDA approves tafasitamab with lenalidomide and rituximab, offering a groundbreaking chemotherapy-free treatment for relapsed follicular lymphoma.
US FDA
The recent FDA approval of tafasitamab-cxix (Monjuvi) in combination with lenalidomide (Revlimid) and rituximab (Rituxan) for relapsed/refractory follicular lymphoma marks a significant advancement in the management of this often relapsing, yet indolent, B-cell malignancy. This chemotherapy-free triplet regimen, supported by the robust findings from the inMIND trial (NCT04680052), offers oncologists a new, highly effective, and well-tolerated option for their patients, particularly those with high-risk disease.1
The approval underscores a growing trend toward targeted and chemo-sparing approaches in indolent lymphomas, aiming to improve long-term disease control and patient quality of life.
Main Findings: A Significant Leap in Progression-Free Survival
The core of this approval lies in the impressive efficacy data from the phase 3 inMIND trial. "Per the results of the inMIND trial, this chemotherapy-free triplet regimen showed a significant reduction in progression risk and a manageable safety profile across a broad like patient population, including high-risk follicular lymphoma," stated Christina Poh, MD, assistant professor, University of Washington, Fred Hutchinson Cancer Center, in an interview with Targeted OncologyTM.
The trial demonstrated a statistically significant improvement in investigator-assessed progression-free survival (PFS) for the tafasitamab arm, with a median PFS of 22.4 months (95% CI, 19.2-not evaluable [NE]) compared with 13.9 months (95% CI, 11.5-16.4) in the control group—an almost doubling of PFS. This translates to a 57% reduction in the risk of disease progression or death (HR, 0.43; 95% CI, 0.32-0.58; P <.0001).2
"We essentially showed improved progression-free survival. This is not just specific to low-risk follicular lymphoma. This is any follicular lymphoma population, including all those high-risk patient populations,” explained Poh. “Those subgroups of [patients with] follicular lymphoma are the subgroups that were historically hard to treat."
This highlights the regimen's potential to benefit a wide spectrum of patients with follicular lymphoma, including those with previously difficult-to-treat characteristics such as those with progression of disease within 24 months and rituximab-refractory disease.
Beyond the positive PFS benefit, the inMIND trial also reported a manageable safety profile. The addition of tafasitamab was not associated with a marked increase in adverse events (AEs), and the treatment was well tolerated in both arms. While overall survival data remains immature, an encouraging trend in favor of the tafasitamab arm has been observed, further reinforcing the potential long-term benefits of this triplet therapy.
Microscopic photorealistic image of T-cell lymphoma cells - Generated with Google Gemini AI
Background on the Approval
Follicular lymphoma is typically an indolent, yet chronic, malignancy characterized by frequent relapses, making durable disease control a critical therapeutic objective. The FDA's decision to approve tafasitamab in combination with lenalidomide and rituximab for adult patients with relapsed/refractory follicular lymphoma provides a much-needed, chemotherapy-free option in this setting.1
This regulatory decision is directly attributed to the robust evidence generated by the inMIND trial. This randomized, double-blind, placebo-controlled study evaluated the triplet regimen against a backbone of lenalidomide and rituximab. The trial enrolled 548 patients with relapsed/refractory follicular lymphoma who had received at least 1 prior systemic therapy. The patient population was designed to reflect real-world disease presentations, with 25% having received 2 prior lines of treatment and 20% having received 3 or more, ensuring the trial's relevance to clinical practice.2
“Patients with relapsed follicular lymphoma were randomly assigned to an investigational arm of tafasitamab/lenalidomide/rituximab vs a control arm of placebo/lenalidomide/ rituximab,” John M. Burke, MD, hematologist/medical oncologist at Rocky Mountain Cancer Centers and associate chair of the US Oncology Hematology Research Program, previously told Targeted OncologyTM.
The primary end point, investigator-assessed PFS, was met with compelling results. With a median follow-up of 14.1 months, the tafasitamab arm demonstrated a clear advantage. Independent review committee assessment further corroborated these findings, reporting a median PFS that was not yet reached (95% CI, 19.3-NE) with the triplet, compared with 16.0 months (95% CI, 13.9-21.1) with the doublet (HR, 0.41; 95% CI, 0.29-0.56; P <.0001). These data, initially presented at the 2024 American Society of Hematology Annual Meeting, underscored the profound impact of tafasitamab on disease progression.
“The addition of tafasitamab markedly improved median progression-free survival, duration of response, and time to next treatment,” added Burke.
The safety profile observed in the inMIND trial aligns with the known AE profiles of CD19-targeted therapies. Serious adverse reactions occurred in 33% of patients receiving tafasitamab, with serious infections reported in 24%. Key warnings and precautions in the product labeling include infusion-related reactions, myelosuppression, and infections. Clinicians are advised to diligently monitor blood counts and infection risk throughout therapy and to manage infusion reactions with appropriate premedication and supportive care.
The recommended dosage of tafasitamab is 12 mg/kg administered via intravenous infusion, with treatment intended for up to 12 cycles in combination with lenalidomide and rituximab.1 It is important to note that this regimen is not approved for use in relapsed/refractory marginal zone lymphoma and is not recommended for such patients outside of clinical trials.
Tafasitamab, a humanized monoclonal antibody targeting CD19, has an established role, having been previously approved in combination with lenalidomide for relapsed/refractory diffuse large B-cell lymphoma. This new indication in follicular lymphoma significantly broadens the therapeutic scope of tafasitamab in B-cell malignancies, offering a valuable chemotherapy-free triplet option for patients who can benefit from an immune-based therapeutic strategy.
Comparing With Existing Regimens and the Role of Dual Targeting
When considering this new triplet, oncologists will naturally compare it with other established chemotherapy-free regimens. Poh acknowledged the challenge of direct comparisons.
"It is hard to compare because we do not have any trial except for with rituximab, which was the comparator arm in this study." She highlights that currently, one of the main approved chemotherapy-free regimens is lenalidomide and rituximab, and the inMIND trial definitively showed a “significant PFS improvement" with the addition of tafasitamab.
Regarding other chemotherapy-free regimens in the relapsed/refractory follicular lymphoma setting, such as bispecific antibodies like mosunetuzumab (Lunsumio)3 or glofitamab-gxbm (Columvi)4, Poh noted, "there have not been any head to head trials looking at this regimen compared with the bispecifics yet." However, she emphasizes a broader perspective for a chronic malignancy like follicular lymphoma.
"The question is not necessarily how this compares. I think the more important question is, how do we sequence these therapies to get the most optimal outcomes?" This insight is crucial for oncologists navigating the evolving landscape of follicular lymphoma treatments, suggesting that the focus should shift from direct head-to-head comparisons to strategic sequencing for maximal patient benefit.
A key aspect of this new regimen is the dual targeting of CD19 (tafasitamab) and CD20 (rituximab). Poh views the inMIND trial as pivotal in addressing the impact of this dual targeting.2
"This inMIND trial is a very important trial to attempt to answer that question, because it is the first to validate this approach of combining 2 monoclonal antibodies, CD19 and anti-CD24, in follicular lymphoma," she explained. While the precise mechanistic interplay at a deeper level requires further research, the clinical benefit is undeniable. "What we are seeing is that the addition of tafasitamab does significantly improve PFS when added to rituximab and lenalidomide...that PFS improvement is very significant.”
Practical Implementation and Guiding Treatment Selection
The practicality of implementing this triplet regimen in a community setting is high, according to Poh. She noted that "tafasitamab is already approved for diffuse large B-cell lymphoma in combination with lenalidomide, so the community providers already are familiar with how to use tafasitamab and its AE profile."
Furthermore, oncologists are well versed in the AE profiles of lenalidomide and rituximab. Poh added, "In the inMIND trial, the addition of tafasitamab did not introduce any new safety concerns or signals," leading to the conclusion that "the addition should be readily adopted in the community."
When considering treatment selection, Poh advised that "all patients benefited, regardless of disease risk." This broad efficacy across subgroups is a notable advantage of the tafasitamab-based regimen, differentiating it from some other treatments where benefits might be more pronounced in specific patient subsets.
"That is not necessarily the case with other regimens. And so, I would say that this can be used in all situations," she said.
For a real-world application, Poh offers clear guidance: "Any patient who one would consider using [lenalidomide] with rituximab should all be considered for this regimen. Clearly this regimen is shown to be superior to [lenalidomide] and rituximab."
She pinpointed lenalidomide as the primary drug to consider in the context of patient comorbidities. "The main drug that physicians think of in terms of comorbidities and whether to utilize this regimen is lenalidomide. So, with that, if we are thinking there are any comorbidities, that is the drug that we would link about in terms of, are there any comorbidities that would be contraindicated with [lenalidomide]? If not, then I think this regimen is reasonable and should be considered."
Future Implications: A Step Towards Chemo-Free Futures
The approval of this tafasitamab-based regimen is more than just another therapeutic option; it represents a key step in the ongoing evolution of follicular lymphoma treatment. Poh reflected on the broader implications, stating, "As we look to the future, there has been this great push to more targeted and more chemotherapy-free approaches in indolent lymphomas. This combination expands our therapeutic arsenal in our efforts to improve long-term disease control and quality of life for patients with follicular lymphoma."
"I do think that this is another important step to achieving that goal where we do not have to use any more chemotherapy, and the treatments that we administer follicular lymphoma are tolerable and effective,” Poh added.
This sentiment captures the promise of tafasitamab in combination with lenalidomide and rituximab, offering a potent, well-tolerated, and chemotherapy-free option that significantly improves outcomes for patients with relapsed/refractory follicular lymphoma. As the understanding of follicular lymphoma pathogenesis deepens and therapeutic strategies evolve, this triplet regimen stands as a testament to the power of targeted, immune-based therapies in transforming the treatment landscape for this chronic malignancy.
