5-year survival data from the Zuma trials shows that there is curative potential in r/r DLBCL with cure rates near 50%.
Axicabtagene ciloleucel induced long-term survival with no new safety signals in patients with refractory LBCL. Durable responses were associated with expansion of chimeric antigen receptor T cells early after intravenous infusion.
In phase 2 of ZUMA-1, a single-arm, multicenter, registrational trial, axicabtagene ciloleucel (axi-cel) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy demonstrated durable responses at 2 years in patients with refractory large B-cell lymphoma (LBCL). Here, we assessed outcomes in ZUMA-1 after 5 years of follow-up. Eligible adults received lymphodepleting chemotherapy followed by axi-cel (2 × 106 cells per kg). Investigator-assessed response, survival, safety, and pharmacokinetics were assessed in patients who had received treatment. The objective response rate in these 101 patients was 83% (58% complete response rate); with a median follow-up of 63.1 months, responses were ongoing in 31% of patients at data cutoff. Median overall survival (OS) was 25.8 months, and the estimated 5-year OS rate was 42.6%. Disease-specific survival (excluding deaths unrelated to disease progression) estimated at 5 years was 51.0%. No new serious adverse events or deaths related to axi-cel were observed after additional follow-up. Peripheral blood B cells were detectable in all evaluable patients at 3 years with polyclonal B-cell recovery in 91% of patients. Ongoing responses at 60 months were associated with early CAR T-cell expansion. In conclusion, this 5-year follow-up analysis of ZUMA-1 demonstrates sustained overall and disease-specific survival, with no new safety signals in patients with refractory LBCL. Protracted B-cell aplasia was not required for durable responses. These findings support the curative potential of axi-cel in a subset of patients with aggressive B-cell lymphomas. This trial was registered at ClinicalTrials.gov, as #NCT02348216.
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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