Variable response rates across chemotherapy regimens for severe idiopathic multicentric Castleman disease.

7082 Background: Idiopathic multicentric Castleman disease (iMCD) is a hematologic disorder treated by oncologists and characterized by diffuse lymphadenopathy and systemic inflammation that can cause multi-organ failure. iMCD subtypes include thrombocytopenia, anasarca, fever, renal dysfunction, and organomegaly (TAFRO) and not otherwise specified. Siltuximab, an interleukin 6 (IL6) antagonist, is the only FDA-approved treatment. For patients with severe disease worsening after siltuximab, consensus guidelines recommend combination chemotherapy though data is limited in guiding chemotherapy selection. Methods: The ACCELERATE registry leverages an expert panel who reviewed medical history and lymph node biopsy slides to rigorously confirm the diagnosis for each patient. To achieve a clinical response, the proportion of abnormal clinical and laboratory criteria assessed prior to regimen initiation has to decrease by at least 50% after regimen initiation. Regimens were grouped based on inclusion of cyclophosphamide, etoposide, doxorubicin, and bortezomib. We quantified response rates and times to next treatment for regimens containing these chemotherapies but statistical comparisons were not possible due to overlapping treatments used across these groups. Response rates for chemotherapy ± IL6 inhibition were compared. Results: We identified 34 (31%) chemotherapy recipients among 111 diagnosis-confirmed iMCD patients: 71% were male, 91% had iMCD-TAFRO; 35 years median age at diagnosis. All iMCD-TAFRO patients met the criteria for severe disease. We found 52 chemotherapy regimens administered to 34 patients. We observed 33 (64%) of the 52 regimens included cyclophosphamide; 23 (44%) etoposide; 21 (40%) doxorubicin; 15 (29%) bortezomib. Regimens were typically given with more than one agent. Twenty-two (42%) were co-administered with anti-IL6. Nineteen (68%) patients had a response if the regimen included cyclophosphamide; 14 (64%) etoposide, 10 (56%) doxorubicin; and 9 (69%) bortezomib. Response rates for all regimens were 60% with IL6 inhibition compared to 64% without. For cyclophosphamide, etoposide, doxorubicin, and bortezomib regimens, median time to next treatment was 9, 4, 4, 6 months, respectively. Conclusions: We found that almost all iMCD patients who received chemotherapy had TAFRO with severe disease. We observed relatively similar response rates across different chemotherapy containing regimens and for patients who received chemotherapy with and without IL6 inhibition. Time to next treatment was longer in the cyclophosphamide group, but this could not be statistically tested. Altogether, we provide the first study of the comparative effectiveness of chemotherapies against iMCD.