Craig Moskowitz, MD, professor, physician-in-chief, Oncology Service Line, Sylvester Comprehensive Cancer Center, University of Miami, discusses the efficacy of several antibody-drug conjugates (ADCs) in diffuse large B-cell lymphoma (DLBCL), how their adverse effect (AE) profiles compare, and how bispecific antibodies are further defining the DLBCL treatment landscape.

Dr. Moskowitz on Tafasitamab Plus Lenalidomide in Relapsed/Refractory DLBCL

Tafasitamab-cxix (Monjuvi) plus lenalidomide (Revlimid) is an easy regimen to use in patients who are not heavily pretreated, Moskowitz says. However, although the combination elicited favorable outcomes in patients enrolled in the phase 2 L-MIND trial (NCT02399085), the real-world patients receiving this regimen as a standard of care are demonstrating lower response rates, Moskowitz notes.

Dr. Moskowitz on Loncastuximab Tesirine in Relapsed/Refractory DLBCL

Loncastuximab tesirine-lpyl (Zynlonta) is an active agent that’s easy to administer, especially now that initial issues with fluid overload and third spacing are more manageable in most patients, Moskowitz says. Patient response can be determined during a 5- to 6-week trial period, and patients who do not respond after 2 cycles are not likely to respond at all, Moskowitz explains. This agent is effective when administered prior to tafasitamab plus lenalidomide, Moskowitz notes.

Dr. Moskowitz on Polatuzumab Vedotin Plus Rituximab in DLBCL

Polatuzumab vedotin-piiq (Polivy) plus rituximab (Rituxan) is an active, well-tolerated combination in DLBCL, and is easier to administer than loncastuximab tesirine, Moskowitz says. Additionally, the phase 3 POLARIX trial (NCT03274492), in which up-front polatuzumab vedotin plus R-CHP (rituximab, cyclophosphamide, doxorubicin, and prednisone) demonstrated a 27% reduction in the risk of disease progression, relapse, or death vs R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), may posit this combination as the first-line standard of care, rather than an option in the second- and third-line settings, Moskowitz emphasizes.

Dr. Moskowitz on Adverse Effects With DLBCL Treatments

The most common AEs that occur with tafasitamab plus lenalidomide, loncastuximab tesirine, and polatuzumab vedotin plus R-CHP are fatigue, fluid third spacing, and neuropathy, respectively, Moskowitz says. However, all 3 of these regimens are generally well tolerated and are fairly simple outpatient therapies, Moskowitz notes.

Dr. Moskowitz on Bispecific Antibodies in DLBCL

Tafasitamab plus lenalidomide, loncastuximab tesirine, and polatuzumab vedotin plus R-CHP have all elicited low complete response rates, making them unideal palliative drugs, Moskowitz says. However, bispecific antibodies appear to be promising in this space, Moskowitz notes. Mosunetuzumab (Lunsumio), which is commonly used in the US, has limited efficacy in large cell lymphoma, but was approved in Europe for relapsed/refractory follicular lymphoma, Moskowitz explains. Additionally, epcoritamab (DuoBody-CDxCD20) and glofitamab are both active bispecific antibodies that, once approved, will likely be used before ADCs in DLBCL, Moskowitz emphasizes.

Dr. Moskowitz on Therapeutic Combinations in DLBCL

Determining how lymphoma drugs work together is crucial, as these agents are not typically used on their own, Moskowitz says. The drugs that are most effective when combined with other active agents are more likely to be used in this arena, Moskowitz concludes.

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Craig Moskowitz, MD, discusses the efficacy of several antibody-drug conjugates in diffuse large B-cell lymphoma, how their adverse effect profiles compare, and how bispecific antibodies are further defining the DLBCL treatment landscape.

Dr. Moskowitz on Antibody-Drug Conjugates in Relapsed/Refractory DLBCL

Craig Moskowitz, MD, physician-in-chief, Oncology Service Line, Sylvester Comprehensive Cancer Center, University of Miami Health System, discusses the use of PET-adapted therapy in the treatment of patients with advanced-stage Hodgkin lymphoma.

Patients will have a pre-treatment PET scan to determine the stage of their disease. After 2 cycles of upfront therapy—which in the United States typically consists of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD)&mdash;patients will undergo another PET scan. If the results of the PET scan are negative, bleomycin is removed from the regimen, after which patients receive 4 months of AVD. Moskowitz notes that this approach is used in about 80% of patients. The other 20% of patients who have a positive PET scan will receive escalated BEACOPP.

These strategies are based on 2 treatment programs, Moskowitz says. One was the RATHL study, which showed that about 78% of patients who have a negative PET scan at interim re-staging are cured. These are encouraging data but not great, he adds. Researchers now know that if patients with a positive PET scan are continued on the same treatment, only about 40% of patients are cured. Since the majority of patients maintain the therapy they were on, still having 20% to 25% of patients not doing well is unfavorable, says Moskowitz.

Craig Moskowitz, MD

Articles

Dr. Moskowitz on Antibody-Drug Conjugates in Relapsed/Refractory DLBCL

Dr. Moskowitz on PET-Adapted Therapy in Advanced Hodgkin Lymphoma