What's New in Hodgkin and Non-Hodgkin Lymphoma

Educational Objectives

The goal of this program is to improve management of Hodgkin and non-Hodgkin lymphoma. After hearing and assimilating this program, the clinician will be better able to:

1. Implement strategies for treating relapsed-refractory Hodgkin and non-Hodgkin lymphoma.
2. Appraise recent evidence-based therapies for mantle cell lymphoma.

Summary

Older patients with CD30-positive classic Hodgkin lymphoma: constitute 15% to 25% of all patients with Hodgkin lymphoma; bleomycin is associated with ≈30% mortality in patients >50 yr of age; clinicians often recommend lower doses and fewer cycles, leading to inferior survival; the SWOG S1826 trial (Herrera et al [2023]) showed that nivolumab with doxorubicin, vinblastine, and dacarbazine (nivo-AVD) yielded superior progression-free survival (PFS) compared with brentuximab vedotin (BV)-AVD; positron emission tomography-adapted approach is recommended if ABVD regimen (bleomycin, doxorubicin, vinblastine, dacarbazine) is used; in the ECHELON trial (Straus et al [2021]), BV-AVD performed better than ABVD, but older patients had poorer outcomes in both treatment groups compared with younger patients; another subset analysis of older patients in SWOG S1826 showed that patients in the nivo-AVD arm had more bulky disease or were older; neuropathy was more common in the BV-AVD arm and neutropenia was more common in the nivo-AVD arm; growth factor prophylaxis was required for the BV-AVD arm but only optional for the nivo-AVD arm; nivo-AVD was associated with superior 1-yr PFS compared with BV-AVD in older patients; nivo-AVD was better tolerated and had a superior event-free survival and overall survival (OS) at 1 yr

Relapsed-refractory follicular lymphoma: mosunetuzumab is approved for use in heavily pretreated follicular lymphoma; it is a bispecific antibody against CD20 and CD3; because step-up dosing can trigger reactions on day 1 of cycles 1 and 2, prophylaxis against cytokine release syndrome (CRS) is indicated (risk is ≈40%); despite advancements in chemoimmunotherapy, patients with relapsed or refractory follicular lymphoma have a poor prognosis, especially after third- or fourth-line therapy; median PFS is ≈1 yr and OS is ≈2 yr; patients with early progression of disease after initial chemoimmunotherapy have a poor prognosis, with a survival rate of ≈50%

Chimeric antigen receptor (CAR) T-cell therapy: has shown promising results for relapsed-refractory follicular lymphoma; axicabtagene ciloleucel and tisagenlecleucel are approved by the US Food and Drug Administration (FDA); long-term follow-up from the ZUMA-5 trial (Neelapu et al [2024]) showed that patients treated with axicabtagene ciloleucel had a high overall response rate (ORR) of 90% and a complete response rate (CRR) of 75%, with responses ongoing at 5 yr; patients in the ZUMA-5 trial were heavily pretreated, and 66% of patients had refractory disease to all prior regimens; lisocabtagene maraleucel (eg, Breyanzi), a new CAR T-cell therapy for diffuse large B-cell lymphoma, uses a prespecified ratio of CD4- and CD8-positive T cells and has shown promising results in clinical trials; the CRR is high, and the therapy is well tolerated (lower incidence of CRS)

Bispecific antibodies: mosunetuzumab is FDA-approved for follicular lymphoma; bispecific antibodies can be obtained off the shelf and have lower risk for CRS, but they must be taken for a long period of time; mosunetuzumab has a step-up dosing regimen that can lead to CRS ≤5 days after the dose; follow-up data at 2 to 3 yr appear to show durable responses; epcoritamab, which is subcutaneously administered, has a step-up dosing regimen that requires premedication with steroids; Thieblemont et al (2023) showed activity in all subgroups of patients with heavily pretreated follicular lymphoma, including those with early progression of disease, double refractory, primary refractory, and refractory to their most recent line of therapy; CRS was significantly reduced through optimized dosing and premedication; odronextamab is given intravenously as 1 dose every 3 wk; it was associated with long PFS in heavily pretreated patients who have a CR

Targeted agents: tazemetostat — an EZH2 inhibitor that is FDA-approved for follicular lymphoma; it has activity independent of mutation status and has shown promising PFS as monotherapy; combinations with lenalidomide and rituximab are currently being tested; zanubrutinib — a Bruton tyrosine kinase (BTK) inhibitor that was previously evaluated in single-arm trials for follicular lymphoma, but showed limited activity and mild toxicity; the ROSEWOOD trial by Zinzani et al (2023) found that zanubrutinib plus obinutuzumab yields superior ORR and CRR compared with obinutuzumab alone in heavily pretreated follicular lymphoma

Relapsed-refractory diffuse large B-cell lymphoma (DLBCL): the timing of relapse and the patient’s fitness level is important; CAR T-cell therapy is superior to autologous transplantation for early relapse; lisocabtagene maraleucel is specifically indicated for older patients with early relapse; epcoritamab and glofitamab are two FDA-approved bispecific agents for relapsed-refractory DLBCL; glofitamab is given intravenously and has a fixed duration of 12 cycles; with glofitamab, pretreatment using obinutuzumab is given to mitigate CRS; initial evaluation showed CRR of 39% and a durable response of >18 mo; updated analysis showed significant differences in PFS and OS; odronextamab is not FDA-approved but shows promise

Mantle cell lymphoma: the SYMPATICO study by Wang et al (2021) showed that venetoclax plus ibrutinib was superior to ibrutinib monotherapy; however, approval of ibrutinib for mantle cell lymphoma has been withdrawn because of toxicity (cytopenia); acalabrutinib has shown promising results as monotherapy for high-risk relapsed-refractory mantle cell lymphoma, with a CRR of 47% and durable responses; pirtobrutinib is a noncovalent BTK inhibitor that does not bind the C481S mutation that mediates resistance to first-generation BTK inhibitors; ORR in relapsed-refractory mantle cell lymphoma was 49%; the median duration of response was 21 mo; CAR T-cell therapy has also demonstrated promising results in mantle cell lymphoma, with high response rates and durable responses

Readings

Herrera AF, LeBlanc M, Castellino SM. et al. Nivolumab (N)-AVD improves progression-free survival compared to brentuximab vedotin (BV)-AVD in advanced stage (AS) classic Hodgkin lymphoma (HL): Results of SWOG S1826. Hematol. Oncol. 2023;41:33–35. doi: 10.1002/hon.3163_5; Neelapu SS, Chavez JC, Sehgal AR, et al. Three-year follow-up analysis of axicabtagene ciloleucel in relapsed/refractory indolent non-Hodgkin lymphoma (ZUMA-5). Blood. 2024;143(6):496-506. doi:10.1182/blood.2023021243; Straus DJ, Długosz-Danecka M, Connors JM, et al. Brentuximab vedotin with chemotherapy for stage III or IV classical Hodgkin lymphoma (ECHELON-1): 5-year update of an international, open-label, randomised, phase 3 trial [published correction appears in Lancet Haematol. 2022 Feb;9(2):e91. doi: 10.1016/S2352-3026(22)00009-6]. Lancet Haematol. 2021;8(6):e410-e421. doi:10.1016/S2352-3026(21)00102-2; Thieblemont C, Phillips T, Ghesquieres H, et al. Epcoritamab, a novel, subcutaneous CD3xCD20 bispecific T-Cell-engaging antibody, in relapsed or refractory large B-cell lymphoma: Dose expansion in a phase I/II trial. J Clin Oncol. 2023;41(12):2238-2247. doi:10.1200/JCO.22.01725; Wang M, Ramchandren R, Chen R, et al. Concurrent ibrutinib plus venetoclax in relapsed/refractory mantle cell lymphoma: the safety run-in of the phase 3 SYMPATICO study. J Hematol Oncol. 2021;14(1):179. Published 2021 Oct 30. doi:10.1186/s13045-021-01188-x; Zinzani PL, Mayer J, Flowers CR, et al. ROSEWOOD: A phase II randomized study of zanubrutinib plus obinutuzumab versus obinutuzumab monotherapy in patients with relapsed or refractory follicular lymphoma. J Clin Oncol. 2023;41(33):5107-5117. doi:10.1200/JCO.23.00775.

Disclosures

For this program, the following relevant financial relationships were disclosed and mitigated to ensure that no commercial bias has been inserted into this content: Dr. Smith has been a consultant at Genmab and Ono Pharmaceutical, and Dr. Smith's spouse has been a salaried employee at Caris. Members of the planning committee reported nothing relevant to disclose. Dr. Smith's lecture contains information related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Smith was recorded at Annual Updates from ASH 2023, held on March 1, 2024, in Chicago, IL and presented by University of Chicago Pritzker School of Medicine. For more information about the upcoming CME activities from this presenter, please visit cme.chicago.edu. Audio Digest thanks the speakers and the University of Chicago Pritzker School of Medicine for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.00 CE contact hours.

Lecture ID:

ON152203

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.