|The following article features coverage from the 2021 American Society of Hematology Annual Meeting. Click here to read more of Cancer Therapy Advisor’s conference coverage.|
Patients with previous use of ibrutinib for chronic lymphocytic leukemia (CLL) who progress with lymphadenopathy have a higher risk of Richter’s syndrome (RS) compared with patients who progress without lymphadenopathy, according to study results presented at the 2021 American Society of Hematology (ASH) Annual Meeting.
Investigators aimed to determine whether clinical characteristics associated with the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria for disease progression predict the risk of RS and overall survival (OS) in patients treated with ibrutinib.
The retrospective study included 559 patients who had received ibrutinib for CLL, of whom 179 (median age, 64 years) progressed according to iwCLL criteria. Of this group, 94% were relapsed/refractory before receiving ibrutinib, and 116 patients progressed on ibrutinib, with a median time to progression after ibrutinib initiation of 40.8 months.
Of the 179 participants who progressed, 54 (median age, 64 years) developed RS — 83% had enlarging lymphadenopathy, 9% had an enlarging liver or spleen, 17% had constitutional symptoms, 31% had increasing lymphocytosis, 15% had worsening thrombocytopenia, 15% had worsening anemia, and 2% had worsening neutropenia. None of the patients had worsening CLL in the bone marrow, and 2% had a new appearance of other organ involvement.
Patients with RS had a median time of 0.4 months (range, 0-49.3) from progression, and 9 patients had biopsy-confirmed RS on the date of progression. The median time from initiation of ibrutinib therapy to RS was 27.8 months (range, 0.7-92.9).
Univariable analysis showed that lymphadenopathy without lymphocytosis at progression was significantly associated with the risk of RS (hazard ratio [HR], 3.58; 95% CI, 1.44-8.88, P =.006).
Among all 179 patients who progressed, 72% had enlarging lymphadenopathy, 10% had an enlarging liver or spleen, 15% had constitutional symptoms, 46% had increasing lymphocytosis, and 15%, 17%, and 2% had worsening thrombocytopenia, anemia, or neutropenia, respectively. Also, 2% had worsening of CLL in the bone marrow, and 1% had new appearance of other organ involvement. In the joint analysis, 45% had lymphadenopathy without lymphocytosis, 20% had lymphocytosis without lymphadenopathy, 26% had both, and 9% had neither.
The median OS from progression was 24.4 months (95% CI, 18.6-45.5), and the median OS from RS diagnosis was 4.0 months (95% CI, 2.1-7.1). The median OS from progression was 15.2 months (95% CI, 7.8-24.6) in those with lymphadenopathy without lymphocytosis and 49.9 months (95% CI, 20.0-NR) in those with lymphocytosis without lymphadenopathy.
Multivariable analysis showed that lymphadenopathy without lymphocytosis remained an independent predictor of OS (HR, 2.12; 95% CI, 1.17-3.87; P =.01).
“Our data suggest that consideration should be given to perform a biopsy to rule out RS in any patients progressing with lymphadenopathy after receiving ibrutinib therapy for CLL,” the researchers concluded.
Disclosures: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
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Kittai AS, Huang Y, Keiter A, et al. Utilizing clinical features of progression to predict Richter’s syndrome in patients with CLL progressing after ibrutinib. Presented at ASH 2021; December 11-14, 2021. Abstract 3731.