This is a nice historical accounting of this sometimes-challenging paradigm. No randomized, prospective trials exist to guide practice management. The question in clinic is often, when to use prophylaxis and when not? The CNS-IPI is the best scoring system validated in the Rituximab era. This did not account for double/triple hit genetics, ABC subtypes or sites of disease (gonads, >3 sites). A high score or any of these groups are generally those that benefit the most from CNS-prophylaxis. The field has moved away from IT-MTX therapy to HD-IV-MTX since most secondary CNSL is parenchymal in nature. Most relapses occur at months 6-9 so sooner is probably better in terms of timing.
CNS relapse in the brain parenchyma, eyes, or leptomeninges is an uncommon but devastating complication of diffuse large B-cell lymphoma. CNS prophylaxis strategies, typically involving intrathecal or high-dose antimetabolites, have been developed in the front-line treatment setting with the aim to reduce this subsequent risk. Clinical and biological features associated with elevated risk are increasingly well defined and are discussed in this Review. This Review summarises both the historical and current developments in this challenging field, provides a nuanced discussion regarding current reasons for and against standard prophylactic measures, outlines evidence for the timing of prophylactic measures when delivered, and reflects on possible future developments.
For transplant-eligible patients with Mantle Cell Lymphoma, Obinutuzumab showed superior efficacy compared to Rituximab. These patients are uncommon, but the results of this study show that in this context O seems to beat R in every aspect, including a 5-yr PFS of 82.8 vs 66.6%, which is striking. I would consider this option for the appropriate patient.
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.
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.
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.
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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