Acalabrutinib-Rituximab Combination Effective in Relapsed/Refractory, Treatment-Naive Follicular Lymphoma

The results show promise for the use of Bruton tyrosine kinase inhibitors in non-Hodgkin lymphoma treatment.

The combination of acalabrutinib (Calquence; AstraZeneca), a non-chemotherapy oral Bruton tyrosine kinase inhibitor (BTKi), and rituximab demonstrated effectiveness and tolerability in patients with relapsed/refractory (R/R) follicular lymphoma (FL) and in those with treatment-naïve (TN) FL, according to results published in the British Journal of Haematology.¹

Microscopic view of high grade follicular lymphoma with marginal zone differentiation

Image credit: © Lisa | stock.adobe.com

For patients administered anti-CD20 antibody-based first-line chemotherapy, there is no guarantee of disease resolution. In fact, 20% of these patients experience disease progression within 24 months, with subsequent treatments being less effective. Investigators have sought to find alternative treatments, centered around BTKis, but results of clinical trials have varied.¹

Since acalabrutinib does not directly impact anti-CD20 antibody-dependent phagocytosis, unlike other agents such as ibrutinib, the second-generation BTKi could be a promising candidate for combination therapy with rituximab, the investigators discussed. Further, showing the potential of the drug, acalabrutinib has shown promise in combination with rituximab in differing indications.^1,2

One such trial, the results of which were presented at the European Hematology Association Congress earlier this year, found that acalabrutinib in combination with bendamustine and rituximab led to statistically significant improvement in progression-free survival (PFS) in patients with untreated mantle cell lymphoma.²

In part 1 of a 3-part, phase 1b/2 multicenter clinical trial (NCT02180711), the investigators conducted an open-label, randomized, parallel-group study evaluating the safety and activity of acalabrutinib, both alone or in combination with rituximab in R/R FL and in combination with rituximab in TN FL.^1,3

A total of 40 patients were enrolled and received treatment, with 12 patients in the acalabrutinib-monotherapy-R/R group, 13 in the acalabrutinib-rituximab-R/R group, and 13 in the acalabrutinib-rituximab-TN group. Two patients enrolled in the original acalabrutinib monotherapy arm discontinued the treatment; therefore, a new randomization schedule was initiated by the investigators to preserve the integrity of the results.¹

About the Trial

Trial Name: Study of Acalabrutinib Alone or in Combination Therapy in Subjects With B-cell Non-Hodgkin Lymphoma

ClinicalTrials.gov ID: NCT02180711

Sponsor: Acerta Pharma BV

Estimated Completion Date: December 29, 2028

The median follow-up duration (95% CI) for those 3 groups, respectively, was 8.1 (2.1, 61.0), 14.3 (1.9, 74.4) and 49.5 (19.5, 79.2) months. In these groups, median acalabrutinib treatment duration was 7.0 (1.8–76.9), 6.0 (0.2–80.1) and 27.6 (1.8–80.7) months, according to reverse Kaplan-Meier analysis. Across all study arms, 22 (55%) patients experienced any grade 3-to-4 treatment-emergent adverse events.¹

For the acalabrutinib-rituximab-TN arm, overall response rate (ORR) and complete response (CR) rate were 92.3% (95% CI, 64.0-99.8) and 38.5%, respectively. In the acalabrutinib-monotherapy-R/R arm, ORR was 33.3% (9.9-65.1) and CR was 8.3%, respectively. Regarding the acalabrutinib-rituximab-R/R arm, ORR was 30.8% (9.1-61.4) and CR was 15.4%, respectively.¹

Positive PFS data was also reported. In the acalabrutinib-rituximab-TN cohort, median PFS was not reached (95% CI, 16.5 months-not estimable [NE]), while in the acalabrutinib-rituximab-TN and acalabrutinib-monotherapy-R/R arms, PFS was 12.0 (1.9-NE) and 8.3 (1.8-NE), respectively. Interestingly, ORR was higher among patients with refractory disease (n = 5; 40.0%, 5.4-85.3) than relapsed disease (n = 15; 33.3%, 11.8-61.6).¹

BTKis had not been previously on the table for R/R FL treatment. However, this new data now suggests the usefulness of these second-generation BTKis in FL, the investigators discussed. Though there were some trial limitations—including the small number of patients enrolled in the trial and the inability to make formal comparisons between groups—this trial sheds light on the possible future of non-Hodgkin lymphoma treatment.¹

“Further studies exploring acalabrutinib in FL are ongoing,” the study authors concluded.¹

REFERENCES

1. Strati P, Champion R, Coleman M, et al. Acalabrutinib alone or in combination with rituximab for follicular lymphoma: An open-label study. BJHaem. 2024. doi:10.1111/bjh.19787

2. McGovern G. Acalabrutinib combination treatment improves progression-free survival in patients with previously untreated MCL. Pharmacy Times. Published June 19, 2024. Accessed October 3, 2024. https://www.pharmacytimes.com/view/acalabrutinib-combination-treatment-improves-progression-free-survival-in-patients-with-previously-untreated-mcl

3. ClinicalTrials.gov. Study of acalabrutinib alone or in combination therapy in subjects with B-cell non-Hodgkin lymphoma. National Library of Medicine. Last Updated July 11, 2024. Accessed October 3, 2024. https://clinicaltrials.gov/study/NCT02180711?tab=history&a=16