At EHA2021 and 16-ICML, there were several relevant presentations in the field of chronic lymphocytic leukemia (CLL) and lymphoma. The first reported on the primary analysis of GLOW, a randomized, phase III trial comparing the time-limited treatment with ibrutinib plus venetoclax, a novel oral combination, versus chlorambucil plus obinutuzumab in treatment-naïve, frail CLL patients.1 The trial was positive, with a significant improvement in progression-free survival (PFS) with ibrutinib plus venetoclax (median, not reached [NR] vs 21.0 months; HR: 0.216 [95% CI: 0.131−0.357]; p<0.0001), despite a relatively short follow-up. The treatment was deemed to be tolerated in this population of older and unfit CLL patients.

The other two studies compared two second-generation Bruton’s tyrosine kinase (BTK) inhibitors, zanubrutinib2 and acalabrutinib,3,4 respectively, with ibrutinib in patients with relapsed CLL. The main takeaway message from these trials is that second-generation BTK inhibitors are better tolerated than ibrutinib, especially in terms of lower rates of cardiac events, which may occur in a fraction of patients treated with ibrutinib. Furthermore, the biomarker analyses of the CLL14 trial have started defining high-risk patients who might not benefit from the combination treatment of venetoclax plus obinutuzumab.5,6 Although results indicated that this time-limited treatment might not be as advantageous for CLL patients with TP53 abnormalities compared with those without these aberrations (median PFS, 49.0 months vs NR), data to draw final conclusions are awaited from the longer follow-up from this trial, as well as from head-to-head studies like CLL17.7

Furthermore, various interesting trials presented at the congresses assessed immunotherapy in lymphomas. Of these, ZUMA-58 and ELARA9,10 investigated chimeric antigen receptor (CAR) T-cell therapies, axicabtagene ciloleucel and tisagenlecleucel, respectively, in patients with follicular lymphoma (FL). There is currently a great unmet medical need in the treatment of this disease as most of the FL patients cannot reach the life expectancy observed in the general population. Indeed, these patients have impaired survival outcomes because of their underlying recurrently progressing and refractory disease. Although the two trials employed two different CAR T-cell products, they both showed that the therapy is well-tolerated and effective in this patient population.8–10 Finally, naratuximab emtansine, an antibody-drug conjugate targeting CD37, in combination with rituximab demonstrated clinical activity in patients with relapsed diffuse large B-cell lymphoma (DLBCL), with an overall response rate of 44.7%, including a complete response rate of 31.6%.11 This is an important signal from the initial results of the trial on this patient population, also with an unmet medical need.