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4574 Retrospective Analysis of Clofarabine Salvage Therapy in Refractory Multifocal Langerhans Cell Histiocytosis (LCH)

Program: Oral and Poster Abstracts
Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Research, Clinical Practice (Health Services and Quality), Clinical Research, real-world evidence, Therapies
Monday, December 11, 2023, 6:00 PM-8:00 PM

Deevyashali Parekh, MBBS1*, Howard Lin1*, Kenneth L. McClain, MD, PhD2, Nitya Gulati1*, Olive S. Eckstein, MD1*, Nader Kim El-Mallawany, MD1, Jennifer Elise Agrusa, MD, MS3* and Carl E Allen, MD1

1Baylor College of Medicine, Houston, TX
2Texas Childrens Cancer and Hematology Centers, Houston, TX
3Texas Children's Hospital, Houston, TX

Purpose: LCH is a neoplastic inflammatory disorder driven by recurrent somatic mutations in the MAPK pathway in myeloid precursors. Over 50% of patients with systemic LCH are not cured with front-line therapies and data to guide salvage options are limited. In this study, we describe 58 patients with relapsed/refractory LCH who were treated with clofarabine.

Methods: Data were extracted from clinical records of patients treated with clofarabine for LCH by Texas Children’s Hospital physicians or collaborators between May 2011 and 2023.

Results: Patients were treated with a median of two chemotherapeutic regimens prior to receiving clofarabine; median age was 3.49 (4 months to 61 years). The typical treatment course was 25mg/m2 daily for 5 consecutive days per month; 19%(11/58) received treatment for less than 6 months; 26%(15/58) for 6-9 months; and 55%(32/58) for 9-24 months. OS in this cohort was 100%(58/58) and PFS was 75% with median 2-year follow-up (range: 5 months to 11 years); The objective response rate (ORR) for all patients was 84% with 9%(5/58) maintaining stable disease and 7%(4/58) developing progressive disease during the study period. Patients treated for LCH-associated neurodegeneration had relatively worse outcomes (ORR: 63%) compared to patients with systemic disease without LCH-ND (ORR: 88%). Patients treated with clofarabine showed significant decreases in the amount of detectable BRAFV600E alleles in their circulating peripheral blood mononuclear cells. Toxicities included cytopenia, vomiting, and bacterial infections, but the majority tolerated chemotherapy in the outpatient setting.

Conclusion: Clofarabine monotherapy has activity against LCH in heavily pretreated patients, the majority of whom achieved durable remission. Prospective multi-center trials are warranted to determine optimal dosing as well as long-term efficacy, late toxicities, relative cost and patient reported outcomes of clofarabine compared to alternative salvage therapy strategies (e.g. MAPK inhibitors) in patients with relapsed/refractory LCH.

Disclosures: Allen: Sobi, Inc: Consultancy.

*signifies non-member of ASH