Second-Line CAR-T Impresses in Transplant-Ineligible Large B-Cell Lymphoma


Therapy with second-line lisocabtagene maraleucel (liso-cel; Breyanzi) yielded a response charge of 80% for sufferers with relapsed or refractory giant B-cell lymphoma (LBCL) who weren’t candidates for hematopoietic stem cell transplant, the part II PILOT study confirmed.
Amongst 61 evaluable sufferers with PET-positive illness, 54% achieved a whole response with the chimeric antigen receptor (CAR) T-cell remedy and 26% had partial responses over a median follow-up of 12.3 months, reported Alison Sehgal, MD, of the College of Pittsburgh Medical Heart in Pennsylvania, and colleagues in Lancet Oncology.
The usual of take care of sufferers with relapsed or refractory LBCL after first-line remedy is salvage chemotherapy adopted by transplant. Nevertheless, not more than half of sufferers are eligible for transplant, with the remaining restricted to non-curative therapies, reminiscent of platinum-based regimens or investigational therapies in medical trials, on account of age, comorbidities, or low efficiency standing, Sehgal and workforce famous.
“Thus, there is a crucial unmet want for efficient second-line therapies for sufferers with relapsed or refractory illness for whom hematopoietic stem cell transplant will not be meant and who don’t have any healing choice,” they wrote.
These findings are according to these from an interim evaluation of the phase III TRANSFORM trial, which confirmed superior outcomes with liso-cel in contrast with normal of care within the second line adopted by transplant in sufferers with relapsed or refractory LBCL.
In June, the FDA approved liso-cel as a second-line therapy for relapsed or refractory LBCL based mostly on the outcomes from each the PILOT and TRANSFORM trials.
In different findings from PILOT, the median progression-free survival (PFS) was 9.03 months at a median follow-up of 13 months, and the median general survival (OS) was not reached at a median follow-up of 17.6 months. The median period of response was 12.09 months at a median follow-up of 15.5 months.
For these sufferers who had a whole response, the median PFS was 22.6 months and the median OS was not reached, whereas the median period of response was 21.7 months.
The most typical grade 3 or larger treatment-emergent adversarial occasions (TEAEs) had been neutropenia (48% of sufferers), leukopenia (21%), and thrombocytopenia (20%). Critical TEAEs associated to liso-cel had been reported in 21% of sufferers, with no treatment-related deaths. Cytokine launch syndrome occurred in 38% of sufferers, and neurological occasions in 31%.
For this open-label research, Sehgal and workforce enrolled 74 sufferers who had obtained first-line therapy containing an anthracycline and a CD20-targeted agent and had been deemed non-candidates for transplant.
All sufferers underwent leukapheresis for manufacture of CAR T cells, and 61 obtained liso-cel from July 2018 to September 2021 at 18 U.S. websites.
Of the 61 sufferers who obtained the CAR T-cell remedy, median age was 74 years, 39% had been girls, 26% had an Japanese Cooperative Oncology Group efficiency standing of two, 54% had refractory illness, 21% relapsed inside 1 12 months of first-line remedy, and 25% relapsed after 12 months of first-line remedy.
Sehgal and colleagues acknowledged a number of limitations to the the research, together with the truth that the median follow-up for OS was comparatively quick at 17.6 months, and longer follow-up is required to find out the survival profit with liso-cel on this affected person inhabitants.
Moreover, focused therapies reminiscent of tafasitamab combined with lenalidomide (Revlimid) and polatuzumab vedotin (Polivy) combined with bendamustine and rituximab have proven efficacy and tolerable security profiles as second-line or later therapy in sufferers with relapsed or refractory LBCL not eligible for transplant, the authors famous.
“If further therapies at the moment being evaluated on this affected person inhabitants present efficacy within the second-line setting, future comparative research with lisocabtagene maraleucel is likely to be needed to find out the relative medical profit to sufferers,” they wrote.

Mike Bassett is a employees author specializing in oncology and hematology. He’s based mostly in Massachusetts.

Disclosures
This research was funded by Juno Therapeutics, a Bristol Myers Squibb firm.Sehgal reported honoraria from OncLive and PeerView Dwell, and analysis funding from Kite/Gilead and Juno Therapeutics. Co-authors reported a number of relationships with business.