Early intervention with lenalidomide may extend time to later therapy in high-risk CLL
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Key takeaways:
- Lenalidomide resulted in a prolonged time to subsequent therapy in high-risk CLL.
- Lenalidomide did not seem to increase the risk for incidence of grade 3 or higher complicating infections and second neoplasms.
Early treatment with lenalidomide resulted in a prolonged time to subsequent therapy in patients with high-risk chronic lymphocytic leukemia, according to extended follow-up data presented at ASH Annual Meeting and Exposition.
Kerry A Rogers, MD, from the division of hematology at The Ohio State University, and colleagues reported long-term results from a phase 2 study to determine the impact of early treatment with lenalidomide on CLL disease course, complicating infections and second neoplasms.
Patients with a high-risk feature — including FISH positive for del(17)(p13.1) and/or del(11)(q22.3), complex karyotype or unmutated IGHV status — no prior treatment and no iwCLL 2008 criteria for treatment began lenalidomide at 2.5 mg daily and increased to 5 mg as tolerated. Researchers assessed OS and PFS from the start and discontinuation of lenalidomide, and calculated time to next therapy from start or discontinuation of lenalidomide to the initiation of next therapy, treating death without new therapy as a competing risk.
Of 49 patients, 94% did not have IGHV mutatations, 47% had complex karyotype, 14% had del(17)(p13.1) and 31% had del(11q)(q22.2), according to the abstract. Median follow-up from start of lenalidomide was 4.6 years and median time on treatment was 3.7 years; two patients remained on lenalidomide at 9.7 and 10.1 years.
Rogers and colleagues found that the median PFS after starting lenalidomide was 5.7 years (95% CI, 3.2-6.4) with an estimated 8-year PFS of 25.9% (95% CI, 13.9-39.6).
In total, 11 patients had progressive disease at the time of lenalidomide discontinuation, with a median time from first dose to progressive disease of 3.7 years. For patients who discontinued without progressive disease, the median PFS from discontinuation was 1.5 years (95% CI, 0.6-2.6). For patients who began a subsequent therapy, the median time to next therapy from starting lenalidomide was 4.4 years and from discontinuing lenalidomide was 1.1 years.
The researchers reported that seven deaths occurred and the median OS was not reached, but the estimated 8-year OS was 73.9% (95% CI, 51.6-87.2).
Lenalidomide did not seem to increase the risk for grade 3 or higher complicating infections and second neoplasms because these complications were as expected for this population, according to the abstract.
Overall, 217 episodes of complicated infections occurred in most patients (88%) and many patients experienced multiple infections (49% had one to three, 39% had more than three infections), according to the results. The most frequent infections included upper respiratory (n = 71), sinus (n = 37), skin and soft tissue (n = 27), and lower respiratory (n = 22). Infections were mild or moderate (grade 1-2) in 95% of cases, but grade 3 or higher infections occurred in 18% of patients who experienced 10 events. The investigators identified nine grade 3 infections as well as a grade 5 infection of COVID-19 in a patient who discontinued lenalidomide more than 2 years previously. The rate of grade 3 or higher infections was 3.8 (95% CI, 1.8-7) per 100-person-years.
In total, eight patients experienced 19 second neoplasms, including nonmelanoma skin cancers (n = 15), lung adenocarcinoma (n = 2 in one patient), melanoma in situ (n = 1) and squamous cell carcinoma (n = 1 in a parotid lymph node from a skin SCC). The researchers reported the rate of second neoplasms was 7.2 (95% CI, 4.3-11.3) per 100-person-years. No cases of acute leukemia occurred.
“In conclusion, lenalidomide can be administered for an extended duration with continued CLL disease control in an early-intervention setting,” Rogers said in the presentation. “Lenalidomide should be further investigated in early intervention and other settings, such as post-therapy maintenance.”
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