Clinical Advances in Hematology & OncologyHighlights in Leukemia and Lymphoma

Commentary by Susan O’Brien, MD, professor of medicine at the University of California, Irvine.

In an array of studies presented recently, novel therapies including nivolumab, axicabtagene ciloleucel, and lisocabtagene maraleucel demonstrate significant advancements in the treatment of lymphomas, including Hodgkin lymphoma, primary mediastinal B-cell lymphoma, and large B-cell lymphoma.

Nivolumab Outperforms Brentuximab Vedotin in Newly Diagnosed Advanced Hodgkin Lymphoma

• Nivolumab plus AVD improved progression-free survival (PFS) and was better tolerated than brentuximab vedotin plus AVD in patients with newly diagnosed advanced HL.
• The phase 3 trial SWOG S1826 enrolled 976 patients who were randomized to receive either nivolumab/AVD or brentuximab vedotin/AVD.
• The 1-year PFS was longer in the nivolumab arm than in the brentuximab vedotin arm, at 94% vs 86% (hazard ratio [HR], 0.48; 99% CI, 0.27-0.87; P=.0005).
• Event-free survival (EFS) was also higher in the nivolumab arm than in the brentuximab vedotin arm.
• Treatment with nivolumab/AVD was well-tolerated, with few immune-related adverse events (AEs).
• There were fewer deaths due to AEs in the nivolumab group compared to the brentuximab vedotin group (3 vs 7).
• Based on the data, nivolumab/AVD is poised to be a new standard for the treatment of advanced HL.

Study Supports Omission of Radiation Therapy in Some Patients With Primary Mediastinal B-Cell Lymphoma

• Patients with PMBCL who experience a complete metabolic response (CMR) after immunochemotherapy may be able to safely omit radiation therapy (RT), according to the IELSG37 trial.
• The trial enrolled 545 patients, of which 268 who achieved a CMR were randomly assigned to observation or mediastinal RT.
• The difference in PFS at 30 months was not statistically significant between the RT arm and the observation arm, and was clinically not relevant.
• The 5-year overall survival (OS) was 99% in both arms.
• There is a need for longer follow-up to examine late toxicity, as RT is known to increase the risk of second malignancies, coronary heart disease, and valvular heart disease.
• Mediastinal RT may be safely omitted in patients with a complete metabolic response after frontline immunochemotherapy containing rituximab and doxorubicin.

Second-Line Axicabtagene Ciloleucel Improves OS in Early Relapsed or Refractory Large B-Cell Lymphoma

• Axicabtagene ciloleucel (axi-cel) significantly improves overall survival (OS) compared with standard of care (SOC) treatment as second-line therapy in patients with early relapsed or refractory large B-cell lymphoma (R/R LBCL), according to the ZUMA-7 trial.
• The trial enrolled 359 patients who were randomly assigned to conditioning chemotherapy plus axi-cel or SOC treatment with platinum-based chemoimmunotherapy.
• Median OS was significantly higher in the axi-cel group than the SOC group (not reached vs 31.1 months, respectively; HR, 0.726; 95% CI, 0.540-0.977; one-sided P=.017).
• The survival benefit favoring axi-cel was similar across prespecified subgroups.
• AEs were consistent with those from the primary EFS analysis.
• ZUMA-7 confirms that axi-cel is a second-line SOC for patients with R/R LBCL and it is the first randomized trial to show an OS benefit for a CAR T-cell therapy over an existing SOC.

Lisocabtagene Maraleucel Demonstrates Durable Responses in R/R CLL/SLL After BTK Inhibition

• Lisocabtagene maraleucel (liso-cel) demonstrated rapid, deep, and durable responses and a manageable safety profile in patients with heavily pretreated, high-risk R/R CLL or SLL.
• The phase 1/2 TRANSCEND CLL 004 study enrolled patients who received at least two prior therapies, including a Bruton tyrosine kinase inhibitor (BTKi).
• At a median follow-up of 12 months, the overall response rate (ORR) was 82%, including a 46% complete response (CR) rate.
• At 12 months, PFS and OS were 77% and 89%, respectively.
• Liso-cel had a manageable safety profile, with no new safety signals identified.
• The TRANSCEND CLL 004 results show that liso-cel has significant activity in patients with R/R CLL/SLL, suggesting its potential use in BTKi-experienced patients.

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