Results presented at the American Society of Hematology annual meeting on Saturday show significant benefits in event-free survival, progression-free survival, and complete response compared to standard of care.
This article has been updated.
Anti-CD therapy with lisocabtagene maraleucel (liso-cel) has shown significant advantages over standard care when given to patients whose large B-cell lymphoma (LBCL) has returned or has not responded ( R / R) to the first treatment after 12 months, according to the interim results of the randomized phase 3 TRANSFORM study.1
“This is a breakthrough therapy that has shown superiority over standard care in terms of efficacy with an extremely favorable safety profile,” said Manali Kamdar, MD, University of Colorado, who presented the results of TRANSFORM on Saturday at the 63rd Annual American Society. of the hematology meeting and exhibition in Atlanta. “We are excited about the potential of this study to change the existing standard of care in these high-risk patients. “
All signs point to liso-cel and another chimeric antigen receptor (CAR) T-cell therapy, axicabtagene cilocleucel (axi-cel), will become the new standard of care for the second-line treatment of patients with of LBCL, given the results for Lisbon and those of the phase 3 ZUMA-7 trial, which were highlighted at a press conference and will be officially presented in plenary on Sunday.
Press conference moderator Laurie Sehn, MD, hematologist-oncologist at the British Columbia Cancer Center for Lymphoid Cancer at the University of British Columbia, called both sets of results “remarkable” and said that they would be welcomed by clinicians who feel limited by the current standard of care.
“I think it’s inevitable that this will become the standard of care,” she said.
Liso-cel, sold as Breyzani by Bristol Myers Squibb, was approved earlier this year for adults who have failed 2 previous treatments for LBCL based on the results of the TRANSCEND-NHL study.2 The researchers reported that its manufacturing process, which results in an equal balance of CD8 + and CD4 + CAR T cells, makes the product more homogeneous and less toxic to patients than the first CAR T cell therapies approved for R / R LBCL.
Using CAR T-cell therapy earlier in a patient’s care journey is a major theme of this year’s ASH meeting. Kamdar’s press briefing just before his presentation explained how liso-cel offered significantly improved measures of survival compared to lifesaving chemotherapy followed by autologous stem cell transplantation, with less toxicity than seen with axi- cel, which was approved in 2017.
In TRANSFORM, 184 patients were randomized to receive liso-cel or the standard of care (SOC). The patients were between 20 and 75 years old; the median age of the SOC arm was 58 years, while the median age of the Liso-Cel arm was 60 years. Two-thirds of the SOC arm were men; the liso-cel arm was 52% female. Patients were well matched by type of non-Hodgkin lymphoma; no racial or ethnic breakdown has been reported.
Median event-free survival (EFS), the primary endpoint of the study, was 2.3 months for SOC versus 10.1 months for liso-cel, for a 65% risk reduction (HR : 0.349; P <.0001 secondary endpoints all favored by liso-cel:>
- The median progression-free survival (PFS) was 5.7 months for SOC versus 14.8 months for liso-cel, for a risk reduction of 59% (RR: 0.406; P = .0001);
- The probability of a complete response was 66% for patients treated with liso-cel, compared to 39% for standard care, for a CR rate that was 27% higher with liso-cel (P <.00001 investigators reported that of the patients who received standard care later liso-cel.>
- The overall survival data was not mature at the time of the data cutoff, but the trend was in favor of liso-cel.
“Despite a relatively short follow-up period of just over 6 months, the positive results of this study suggest that CAR T cell therapy has the potential to become the new standard of care for patients who do not respond to the drug. initial chemotherapy or relapsing. within 12 months, ”Kamdar said.
She pointed out that the patients in the study were at very high risk; by current standards of care, many do not succeed with a stem cell transplant – in contrast, as a second line, most have received an infusion of liso-cel. This contrasts with the situation when patients are in advanced stages of treatment – a major challenge is that patients may be too sick to wait until the CAR T cell manufacturing process is complete.
“Of the patients randomized to receive standard care, only 46% were able to proceed with a transplant,” Kamdar said. “On the other hand … 97% of patients are able to successfully receive the liso-cel infusion.”
Adverse events. From a safety point of view, liso-cel was comparable to SOC, and some patients may have received CAR T-cell therapy on an outpatient basis. Although the well-known effects associated with CAR T cell therapy of cytokine release syndrome (CRS) and neurological toxicity were observed, there were no grade 4 or 5 neurological events. No deaths were observed. was attributable to treatment with liso-cel.
The investigators did not report any new safety signals from liso-cel during the administration of the second-line treatment. About half (49%) of people receiving liso-cel had some level of CRS, 37% reporting grade 1 and 11% reporting grade 2; 1 patient reported grade 3 effects which started on day 9 after treatment and resolved within 2 days. The patients were treated with tocilizumab (24%) and corticosteroids (17%). The most common AEs with treatment were cytopenias, which were reported in 43% of patients.
The conclusions are logical. “For someone who has to treat large B cell lymphoma patients like I do, it is incredibly frustrating when patients [have] first line therapy failed, ”she said. For TRANSFORM and ZUMA-7 patients, who are at particularly high risk – Sehn called them “the worst of the worst” – the current approach calls for doubling with higher doses of chemotherapy. Patients continue to fail, she said.
Thus, “it is not surprising that the arrival of a new approach and of a cell therapy which has proven its curative capacity [in the] third-line setting, you may have outperformed by coming up with more chemotherapy, ”Sehn said.
The word that comes to my mind, she said, is that the conclusions are “logical.”
1. Kamdar M, Solomon SR, Arnason JE, et al. Lisocabtagene maraleucel, a chimeric antigen receptor T cell therapy directed against CD19, versus standard treatment with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with large B-cell lymphoma in relapse or refractory: results of phase 3 randomized transform study. Presented at the 63rd ASH Annual Meeting; December 11, 2021; Atlanta, Georgia. Accessed December 11, 2021. https://bit.ly/30KxmfW
2. Abramson JS, Palomba ML, Gordon LI et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphoma (TRANSCEND NHL 001): a multicenter study of transparent design. Lancet. 2020; 396 (10254): 839-852. doi: 10.1016 / S0140-6736 (20) 31366-0