There are too many options for DLBCL now with monoclonal antibodies, bispecific and CAR-T therapy, but in frail patients, this might be an option. Tafatistamab with lenalidomide had higher ORR (55vs 50) and CR( 37 vs 27%) but this is comparing different trials, and this trial had mostly elderly pts, I do feel tafatistamab is fairly well tolerated though. But when in doubt this seems to be a fair option.
Treatment of diffuse large B-cell lymphoma (DLBCL) in older patients is challenging, especially for those who are not eligible for anthracycline-containing regimens. Fondazione Italiana Linfomi (FIL) started the FIL_ReRi study, a 2-stage single-arm trial to investigate the activity and safety of the chemo-free combination of rituximab and lenalidomide (R2) in ≥70-year-old untreated frail patients with DLBCL. Frailty was prospectively defined using a simplified geriatric assessment tool. Patients were administered a maximum of 6 28-day cycles of 20 mg oral lenalidomide from days 2 to 22 and IV rituximab 375 mg/m2 on day 1, with response assessment after cycles 4 and 6. Patients with partial response or complete response (CR) at cycle 6 were administered lenalidomide 10 mg/d from days 1 to 21 for every 28 cycles for a total of 12 cycles or until progression or unacceptable toxicity. The primary end point was the overall response rate (ORR) after cycle 6; the coprimary end point was the rate of grade 3 or 4 extrahematological toxicity. The ORR was 50.8%, with 27.7% CR. After a median follow-up of 24 months, the median progression-free survival was 14 months, and the 2-year duration of response was 64%. Thirty-four patients experienced extrahematological toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events grade ≥3. The activity of the R2 combination was observed in a significant proportion of subjects, warranting further exploration of a chemo-free approach in frail older patients with DLBCL. This trial was registered at EudraCT as #2015-003371-29 and clinicaltrials.gov as #NCT02955823.
This combination had impressive results but led to a high rate of ventricular arrythmias (9%), hence the combination is not recommended. Another study with the combination and rituximab was also suspended, the etiology of the higher rate of Vent arrhythmias is not known. This combination in another lymphoid malignancies did not lead to that rate of toxicity.
This gives more credence to the idea of avoiding bendamustine before CAR T therapy. Patients exposed to bendamustine had about a 20% lower overall response rate (ORR), 50% shorter progression-free survival (PFS) and >50% shorter overall survival (OS) compared to those who were bendamustine naive. Although other factors may also play a role here, these seem to be significant differences and should make it clear that one should not use this drug before pursuing CAR T therapy.
Good review of high-risk patients, showing that prophylactic high dose MTX did not have lower risk of CNS disease.
Final results from the ASPEN study confirm the strong long-term superiority of zanubrutinib over ibrutinib in symptomatic WM. While overall survival (OS) and progression-free survival (PFS) end-points are still to be reached, demonstrating the good prognosis of this disease, toxicities and response rates are much better with zanubrutinib. This is a cat-1 indication oof NCCN and a compelling option for use in this population.
Speaking of tafatistamab, it seems it is fairly tolerable in first line with almost 75% CR added to RCHOP, adding lenolidomie 86% CR, but this is a phase 1b. Awaiting phase 3 data, we may have another first line option or may the first line option.
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