The US Food and Drug Administration (FDA) recently licensed tafasitamab-cxix (Monjuvi) in combination with lenalidomide for the medication of adults with relapsed or refractory diffuse sizable B-cell lymphoma (DLBCL) now not in any other case specified, including DLBCL coming up from low-grade lymphoma, who’re now not eligible for autologous stem cell transplant (ASCT).
To gain out extra about this drug and its approval, Medscape reached out to Ann S. LaCasce, MD, a lymphoma specialist, companion professor of substances at Harvard Medical College, and director of the Dana-Farber/Massachusetts Long-established Brigham fellowship in hematology/oncology.
Dr Ann S. LaCasce
Medscape: How frequent is relapsed or refractory DLBCL? Have there been any changes in the rates of this disease in most contemporary years?
LaCasce: Roughly 40% of patients with DLBCL would perchance maintain relapsed or refractory disease. The rates of lymphoma were rising over the past loads of decades for unclear causes. As here’s a disease predominantly of older adults, rising lifestyles expectancy seemingly performs a job. Environmental factors can also additionally be contributing.
How long form patients with relapsed or refractory DLBCL who’re now not eligible for stem cell transplant generally continue to exist?
Here is extremely variable, though or now not it is estimated to be approximately 1 twelve months. Some patients will seemingly be cured with autologous transplantation or CAR-T cells. The tear of the disease can also additionally be highly variable, with some patients responding to loads of traces of therapy whereas others can even maintain in an instant revolutionary refractory disease.
What makes patients with relapsed or refractory DLBCL ineligible for ASCT?
In recount to be eligible, patients must gathered be younger than 70 to 75 years or so without essential comorbidities and will must maintain chemotherapy-responsive disease. Extra than half of patients will now not fit these standards.
Are you able to temporarily represent the L-MIND seek for that ended in the approval of tafasitamab-cxix?
This was a single-arm, fragment 2 seek for of tafasitamab plus lenalidomide in patients with relapsed/refractory DLBCL role after one to 3 prior regimens who weren’t candidates for ASCT. Patients obtained tafasitamab unless progression and as a lot as 1 twelve months of lenalidomide. The median age was 72 years, and 50% of patients had obtained supreme one prior line of therapy.
The total and complete response rates in 80 patients treated were 60% and 43%, respectively. The median progression-free survival was approximately 1 twelve months. Practically half of patients required dose reduction of lenalidomide, and a few quarter discontinued the drug. Twenty-five percent of patients discontinued therapy for detrimental events.
What’s the toxicity profile of tafasitamab-cxix?
Essentially the most frequent detrimental events were infusion reactions and myelosuppression, which can also very effectively be managed with identical outdated approaches to incident price ratios with steroids, antihistamines, etc. Myelosuppression can occur, nonetheless on this combination is basically driven by lenalidomide, which is dose diminished or discontinued.
Where does tafasitamab-cxix slot in the medication paradigm for relapsed or refractory DLBCL? How does it evaluate with diversified available ideas?
Here is an option for patients who’re now not candidates for potentially curative approaches, including ASCT and CAR T-cell therapy. There are patients now not eligible for ASCT who can also be acceptable for CAR-T.
Tafasitamab plus lenalidomide requires frequent visits, in particular right thru the first 3 months, after which each and every diversified week unless progression. The dose of lenalidomide is presumably now not tolerable for many of these patients.
A quantity of ideas on this population consist of polatuzumab plus bendamustine/rituximab or presumably selinexor. The broken-down has the same teach and is time restricted, though many patients will now not tolerate the pudgy dose of bendamustine. In the seek for main to approval, selinexor had a worthy lower response price of approximately 30%, and the affected person population was worthy extra favorable, offered that eligibility required 60 to 98 days after final therapy sooner than enrolling.
The supreme approval train for nontransplant patients is tafasitamab/lenalidomide.
From a fee standpoint, how does tafasitamab evaluate with diversified ideas on this affected person population?
I set now not need accurate figures, nonetheless all ideas are very costly. CAR-T is the most costly. Given the continued therapy of tafasitamab unless progression, the cumulative fee can also be very high. Polatuzumab plus bendamustine/rituximab and selinexor are also very costly.
What diversified drugs are in kind for relapsed or refractory DLBCL?
Unusual CAR T-cell therapies, including lisocabtagene maraleucel that’s on the FDA, are in kind. Bispecific antibodies (REGN1979 and mosunetuzumab), combos with CD47 antibodies, and loncastuximab tesirine are all in fragment 2 trials.
LaCasce has disclosed no linked monetary relationships.
Kate O’Rourke is a contract creator in Portland, Maine. She has covered the discipline of oncology for over 10 years.
For added files, educate Medscape on Fb, Twitter, Instagram, and YouTube.
