Practical Considerations, Future Outlook for Linvoseltamab in Multiple Myeloma Care: Hans Lee, MD

Following its July 2 FDA approval, Hans Lee, MD, director of myeloma research at Sarah Cannon Research Institute and investigator on the phase 1/2 LINKER-MM1 trial (NCT03761108), shares key practical considerations for clinicians incorporating linvoseltamab into treatment plans for patients with heavily pretreated multiple myeloma. He also highlights ongoing clinical trials that are exploring linvoseltamab's potential in various settings, offering a preview of its evolving role in multiple myeloma care.

Watch part 1 of the interview to learn more about the LINKER-MM1 data supporting the approval and how linvoseltamab may benefit this patient population.

This transcript was lightly edited; captions were auto-generated.

Transcript

What practical considerations should clinicians keep in mind as they begin incorporating linvoseltamab into their treatment approach?

I think there [are] a couple of aspects around this question. I think the first aspect is that as clinicians get prepared to incorporate linvoseltamab in their clinical practice, there is this concept of step-up dosing that's, again, common with all BCMA [B-cell maturation antigen] bispecific antibodies, where a patient may receive a low dose of 5 mg for the first dose, a second intermediate step-up dose of 25 mg 1 week thereafter, and the first target dose of 200 mg on week number 3.

Again, there is a 24-hour hospitalization recommendation after the initial first 2 step-up doses. During this period of time, there is also monitoring for cytokine release syndrome (CRA), potential [immune effector cell–associated neurotoxicity syndrome], and other immune effector cell [adverse] effects.

The risk for CRS is low, so the majority of CRS is really grade 1, which is fever, which is easily manageable, but these are things that clinicians need to be mindful of when initially dosing linvoseltamab.

On the back end, the thing to keep in mind is the potential risk for infections. Like other BCMA bispecific antibodies, there are higher rates of infection, perhaps compared with some other standard myeloma therapies. Being very vigilant and proactive about infection mitigation strategies [is necessary].

This would include [intravenous immunoglobulin], for instance, as primary prophylaxis to mitigate the risk of infection. To keep the [immunoglobin G] levels more than 400, infection prophylaxis with valacyclovir [or] acyclovir for shingles prophylaxis or [varicella-zoster virus] prophylaxis, as well as [Pneumocystis jirovecii pneumonia] prophylaxis, is mandatory for patients receiving this drug.

Looking ahead, what role do you see linvoseltamab playing in the multiple myeloma treatment landscape, whether in earlier lines of therapy, as part of combination strategies, or beyond?

Linvoseltamab is being studied in multiple settings in multiple myeloma through various clinical trials. Probably most importantly, the LINKER-MM3 (NCT05730036) study is a phase 3 randomized study evaluating linvoseltamab vs a standard of care therapy, elotuzumab [plus] pomalidomide and dexamethasone. This is the confirmatory phase 3 study that will support the accelerated approval of linvoseltamab from the LINKER-MM1 study.

Linvoseltamab is also being studied, for instance, in newly diagnosed myeloma. The LINKER-MM4 (NCT05828511) study is looking at linvoseltamab as a monotherapy, both in transplant-eligible and transplant-ineligible [patients with multiple] myeloma. I think, generally speaking, we have a lot of optimism that BCMA bispecifics will be utilized in the frontline setting eventually in [patients with] multiple myeloma given their high efficacy in relapsed/refractory disease. That'll be a very important study, and we will look forward to seeing the readout of those initial results, hopefully soon.

Also, linvoseltamab is being studied in combination as well. In myeloma, we often combine active drugs with other active drugs. The LINKER-MM2 (NCT05137054) study is a very important study, again, looking at linvoseltamab in combination with other agents active in multiple myeloma. Initial results of several arms of the LINKER-MM2 study, for instance, linvoseltamab in combination with carfilzomib and in combination with bortezomib, were presented at this year's [American Society of Clinical Oncology] and [European Hematology Association] meetings.

It's safe to combine linvoseltamab with these agents, and early efficacy is also being demonstrated as well. Again, there are a lot of clinical trials combining linvoseltamab in multiple settings in multiple myeloma, and I think this will be very important in the coming years to see these results.