Oral Bruton tyrosine kinase inhibitors make notable strides in CLL treatment. Chimeric antigen receptor T-cell therapy continues to command attention by besting standard-of-care therapies.
Acalabrutinib Provides Long-Term Survival Benefits vs Standard of Care in Relapsed/Refractory CLL
Treatment with acalabrutinib (Calquence) for relapsed/refractory chronic lymphocytic leukemia was effective out to 3 years and demonstrated a progression-free survival (PFS) benefit over standard of care, according to a 3-year follow-up of the ASCEND study (NCT02970318). 1
Long-term follow-up data from ASCEND, which were presented by Wojciech Jurczak, MD, PhD, head of the Department of Hematology at Maria Sklodowska-Curie National Research Institute of Oncology in Kraków, Poland, also demonstrated that acalabrutinib was well tolerated with no new safety findings.
During follow-up, patients treated with acalabrutinib monotherapy had significantly prolonged PFS compared with those treated with idelalisib (Zydelig)/rituximab (Rituxan) or bendamustine (Bendeka)/rituximab (median, not reached [NR] vs 16.8 months; HR, 0.29; 95% CI, 0.21-0.41; P < .0001). More patients in the acalabrutinib group achieved 36-month PFS compared with those in the investigator–selected treatment group (63% vs 21%). When investigators assessed the groups separately, they observed similar benefits regarding PFS when comparing acalabrutinib with idelalisib/rituximab (median, 16.2 months; HR, 0.31; P < .0001) and with bendamustine/rituximab (median, 18.6 months; HR, 0.25; P < .0001).
“Overall, these data support the use of acalabrutinib in patients with relapsed/ refractory chronic lymphocytic leukemia, including those with high-risk features,” Jurczak said during the presentation.
Ibrutinib Plus FCR Shows Encouraging Activity as Time-Limited Option for Younger Patients With CLL
The addition of ibrutinib (Imbruvica) to fludarabine, cyclophosphamide, and rituximab (Rituxan; iFCR) resulted in a higher rate of complete responses (CRs) with bone marrow undetectable minimal residual disease (BM-uMRD) in younger, fit patients with chronic lymphocytic leukemia (CLL), according to long-term data from a phase 2 study (NCT02251548).1
Moreover, these results included patients with unmutated IGHV, a population who rarely has durable responses, according to Matthew S. Davids, MD, MMSc, director of clinical research in the Division of Lymphoma at Dana-Farber Cancer Institute and an associate professor of medicine at Harvard Medical School.
“Other studies have suggested that patients treated with ibrutinib-based therapy have variable benefits, even with IGHV-unmutated disease. However, we have not seen larger data yet for the combination of ibrutinib with FCR,” said Davids during a presentation of the data. “We hypothesized that combining ibrutinib with FCR as initial therapy would lead to a high rate of CR with BM-uMRD in a broad population of younger, fit patients [with CLL].”
The median number of ibrutinib maintenance cycles was 24 (range, 0-81). In the intent-to-treat (ITT) population, the rate of CR with BM-uMRD improved to 55% (n = 47) and the best rate of BM-uMRD remained at 84% (n = 71). The CR rate deepened with ibrutinib maintenance therapy, from 34% to 81% as the best rate. This was similar among the IGHV-mutated and -unmutated patients, up from 41% to 88% and up from 28% to 76%, respectively, as the best rates. Lastly, the BM MRD-negative rates in the ITT population were 91% in the 81 patients with the TP53 mutation. With the time-limited novel agent plus chemoimmunotherapy, 3-year progression-free and overall survival rates were 97% and 99%, respectively. Thirteen patients (21.3%) who discontinued ibrutinib have had recurrent BM-MRD, including 5 patients with clinical progression of CLL. Seven patients restarted treatment with ibrutinib, all of whom have experienced partial responses. The median time on retreatment is 12.8 months (range, 4.2-26.2).
Cilta-Cel Continues to Impress With Durable and Deep Responses in Relapsed/Refractory Multiple Myeloma
Ciltacabtagene autoleucel (cilta-cel) elicited a 97.9% objective response rate (ORR) and an 82.5% stringent complete response (sCR) rate in patients with relapsed/refractory multiple myeloma at a median of approximately 2 years of follow-up, according to updated findings from the phase 1b/2 CARTITUDE-1 trial (NCT03548207).1
Additionally, the 2-year progression-free and overall survival (OS) rates were 60.5% and 74.0% in all patients, respectively, and minimal residual disease (MRD) negativity was achieved in 92% of evaluable patients for MRD (n = 61). The 2-year progression-free survival (PFS) rates were improved in those who had MRD negativity sustained for at least 6 and 12 months, at 91% and 100%, respectively, as well as the 2-year OS rates at 100% and 100%.
“These data are encouraging, and they suggest that cilta-cel will be an important treatment option for patients with multiple myeloma,” said lead study author Thomas Martin, MD, a clinical professor of medicine in the Adult Leukemia and Bone Marrow Transplantation Program, and associate director of the Myeloma Program at the University of California, San Francisco, in a presentation on the data.
Cilta-cel is a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy with 2 BCMA-targeting single-domain antibodies that are designed to confer avidity. A biologics license application seeking approval for the agent is currently under priority review with the FDA for its use in adult patients with relapsed and/or refractory multiple myeloma. 2
In November 2021, the FDA extended the Prescription Drug User Fee Act target date for the application to review recently submitted data linked with an updated analytical method following the agency’s request for information request that was issued by the agency.2 The new action date is February 28, 2022.
Liso-Cel Outperforms Standard Therapy in Improving QoL in Relapsed/Refractory LBCL
Lisocabtagene maraleucel (liso-cel; Breyanzi) fostered a better quality of life (QOL) in patients with relapsed/refractory large B-cell lymphoma (LBCL) compared with current standard of care (SOC), according to data from a comparative analysis of the phase 3 TRANSFORM trial (NCT03575351).1
Evaluable patients who received the chimeric antigen receptor (CAR) T-cell therapy (n = 47) experienced a mean change in cognitive functioning of 2.21 (range, –1.48 to 5.90) vs –2.09 (range, –6.00 to 1.83) in those who received SOC (n = 43); this translated to a difference of 4.30 (range, –0.76 to 9.36) on day 126 from baseline.
Those in the liso-cel arm also experienced a mean change in fatigue of –1.95 (range, –7.40 to 3.51) compared with 3.75 (range, –2.17 to 9.68) in the SOC arm, equating to a difference of –5.70 (range, –13.24 to 1.84) on day 126 from baseline. In these domains, the liso-cel group improved, whereas the SOC group deteriorated.
The liso-cel group also experienced mean changes in physical functioning and pain of –2.75 (range, –6.76 to 1.25) and –11.14 (range, –16.37 to –5.92), respectively, compared with –2.17 (range, –6.64 to 2.30) and –15.56 (range, –21.25 to –9.88), respectively, for the SOC group. The differences between the 2 arms in physical functioning and pain were –0.58 (range, –6.17 to 5.01) and 4.42 (range, –2.72 to 11.56), respectively.
“Overall QOL was either improved or maintained from baseline in patients with relapsed/refractory LBCL who received liso-cel as second-line treatment,” presenting study author Jeremy Abramson, MD, director, Jon and Jo Ann Hagler Center for Lymphoma, associate professor of medicine, Massachusetts General Hospital Cancer Center, said during a presentation of the data. “These findings corroborated with previously reported health-related QOL associated with liso-cel treatment.”