Is a cell-depleting DMT safe prior to HSCT?


Long-acting disease-modifying therapies do not appear to increase the risk of complications following autologous hematopoietic stem cell transplantation (aHSCT), according to a retrospective study from Sweden (Kvistad et al. J Neurol Neurosurg Psychiatry 2022;93:844-848).

The research question was whether cell-depleting therapies (rituximab, cladribine, alemtuzumab), which can produce prolonged cytopenias, increase the risk of infections or other complications when administered prior to aHSCT.

The study examined data for 104 MS patients (mean age 30.8 years) who had received a DMT <6 months prior to undergoing aHSCT in the period 2011-2021. Mean duration of MS was 5.8 years. Median EDSS score at baseline was 3.0 (range 0-6.5). The mean number of prior DMTs was 2.1; 11.5% patients were previously untreated (aHSCT is a first-line option in Sweden) and 16.3% had received >4 DMTs.

The last treatment in the six months before aHSCT was no DMT (24%); injectables (10%); natalizumab (19%); fingolimod (14%); oral first-line agent (8%); rituximab (17%); alemtuzumab (6%); and cladribine (2%). The mean follow-up time was 39.5 months.

With respect to early adverse events, 66% developed neutropenic fever; the incidence was 29% in the subgroup who had received a cell-depleting DMT. Serious adverse effects were septic febrile neutropenia and EBV reactivation in one patient who had received natalizumab, one case of thoracic venous thrombosis in a patient who had received fingolimod, and a case of fever and psychosis in a patient who had received no DMT.

Late complications included secondary autoimmunity in 19% of patients. The rate was 15% in patients who had received a cell-depleting DMT; this included two alemtuzumab patients who developed hyperthyroidism. The rate of autoimmunity among those without recent DMT exposure was 7%. Between-group differences were not significant.

Following aHSCT, 19% showed evidence of disease activity at three years, including three patients with sustained disease progression (baseline 4.0-5.5 increasing 1-3 points). All patients who had received a cell-depleting DMT achieved NEDA-3 (no relapses, EDSS progression or new MRI lesions).

A small case series previously reported no excess toxicity in alemtuzumab-treated patients who later received aHSCT (Boffa et al. Mult Scler 2021;27:1145-1148).

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