What AEs Should Physicians Be Aware of With Bispecifics in Indolent Lymphoma?

As new therapies for indolent lymphomas are developed and implemented into care, new toxicities often emerge. One of the more recent emergences with novel immunotherapy combinations, particularly those including bispecific antibodies, in indolent lymphoma care has been infections.

Following his presentation titled “Novel Immunotherapy Combinations in Indolent Lymphoma”, Lorenzo Falchi, MD, spoke with CancerNetwork® at the Society of Hematological Oncology (SOHO) 2025 Annual Meeting.

When prompted about the most pressing toxicities care providers must take into consideration when treating patients, Falchi, an oncologist and hematologist specializing in lymphoma at the Memorial Sloan Kettering Cancer Center (MSKCC), highlighted infections, including respiratory, viral, and bacterial infections.

At MSKCC, he noted that when treating with bispecifics, those patients will receive prophylaxis or another agent to reduce the harmful effects of the toxicity. They are also quick to use intravenous immunoglobulin.

Additionally, recent data have suggested that there is a non-relapse mortality risk with bispecific antibodies that is driven by infections, and that is just another reason why physicians must remain aware and cautious of the safety profile of these agents.

Transcript:

What has been an emergent toxicity that initially we have not talked about enough, but now what we are all keenly aware of—and [Dr. Laurie H. Sehn, MD, MPH], gave a wonderful presentation associated with warnings of this toxicity, is infectious disease complications or infections. Most of these infections are respiratory infections, viral infections, bacterial infections, or anything [derived] from sinusitis to pneumonia. These patients are at risk of those infections, and there is no well-established or agreed-upon algorithm or guideline on how to best manage these.

Each center has its own experience. In our own experience, for example, when we start a patient on a bispecific antibody for a recurrent lymphoma, we will ensure these patients have a [Varicella-Zoster Virus (VZV)] prophylaxis with acyclovir or valacyclovir, or a [pneumocystis jirovecii Pneumonia (PJP)] prophylaxis with [trimethoprim-sulfamethoxazole] or similar drugs. We will have a low threshold to use intravenous immunoglobulin replacement because most of these patients, [due to] their previous history and because of the bispecific itself, will have a low level of IgG. Oftentimes, that is associated with recurring infections, not just one episode.

We will use G-CSF or growth factor support whenever we encounter a neutropenia of grade 3 or higher, and, in general, will be aware and [alert] for these potential infections because there’s emerging data that suggests that there is a non-relapse mortality [risk] associated with bispecific antibodies, and that’s primarily driven by infections. We want to make sure that we are aware of that complication and that we manage it promptly [or] prevent it if we can.

References

Falchi, L. Novel immunotherapy combinations in indolent lymphoma. Presented at the Society of Hematological Oncology 2025 Annual Meeting; September 2-6, 2025; Houston, TX.