Ruxolitinib may prove to be an effective treatment of parkinsonism arising from ciltacabtagene autoleucel treatment for patients with multiple myeloma, according to the results of a case report published in the Journal of Hematology. The report featured two cases of patients with multiple myeloma who were treated with ciltacabtagene autoleucel and developed immune effector cell–associated hemophagocytic lymphohistiocytosis–like syndrome (IEC-HS) and parkinsonism; treatment with ruxolitinib was found to effectively control their symptoms.
Treatment with B-cell maturation antigen (BCMA)–targeted chimeric antigen receptor (CAR) T-cell therapy can lead to movement and neurocognitive treatment-emergent adverse events, including parkinsonism. As a distinct pathogenesis has been found between ciltacabtagene autoleucel–associated parkinsonism and Parkinson’s disease, standard Parkinson’s treatments, such as carbidopa/levodopa, have not been effective for these patients. Thus far, minimal responses have been seen with other traditional therapies used for adverse events, such as corticosteroids or chemotherapy, as well as immunosuppressive therapies.
“As CAR T-cell therapy for [multiple myeloma] is expanding and moving to earlier lines, the need to optimize therapy for parkinsonism, a potentially life-threatening complication, becomes more urgent,” study authors Baldeep Wirk, MD, and Jin Lim, MD, PhD, both of Virginia Commonwealth University, wrote in their case report.
Case 1
The first patient was a 53-year-old female with stage I kappa light chain multiple myeloma with del(17p13) and a DNMT3A mutation. She was treated with lenalidomide, bortezomib, carfilzomib, pomalidomide, and daratumumab for more than 3 years and became pentarefractory. She was then treated with ciltacabtagene autoleucel with standard lymphodepleting chemotherapy.
At day 6 after infusion, she developed grade 2 cytokine-release syndrome, which resolved with two doses of tocilizumab; on day 10, she developed IEC-HS. She was treated with anakinra, dexamethasone, and cryoprecipitate, and the transaminitis resolved; however, the hypofibrinogenemia, hyperferritinemia, and pancytopenia did not.
At day 30, she developed hypomimia, hypophonia, cogwheel rigidity, micrographia, bradykinesia, inability to stand without assistance, and shuffling gait. Brain magnetic resonance imaging (MRI) showed increased T1 signaling of the bilateral basal ganglia, which was not evident prior to ciltacabtagene autoleucel treatment. Fludeoxyglucose-18 positron-emission tomography (FDG-PET) indicated hypometabolism of the caudate and frontal lobes. She was diagnosed with stage IV ciltacabtagene autoleucel–associated parkinsonism.
Intravenous gammaglobulin and methylprednisolone were prescribed, without any improvement of the parkinsonism. Salvage ruxolitinib at 5 mg twice daily was initiated on day 95 because of the IEC-HS; within 3 weeks, the micrographia, cogwheel rigidity, bradykinesia, hypomimia, and hypophonia resolved. Another brain MRI at day 157 showed resolution of the T1 signaling in the basal ganglia. The ruxolitinib dose was increased to 10 mg twice daily, and the patient did not develop any infections.
The patient resumed normal activities and achieved a stringent complete remission with measurable residual disease at day 100, which was sustained 1 year after CAR T-cell infusion.
Case 2
The second patient was a 70-year-old male with stage I IgA kappa multiple myeloma with del(17p13), del(1p36), and del(14q32). He was treated with daratumumab, lenalidomide, bortezomib, dexamethasone, salvage pomalidomide, and ixazomib. He then received standard lymphodepleting chemotherapy prior to ciltacabtagene autoleucel.
At day 8, the patient developed grade 1 cytokine-release syndrome, which resolved with two doses of tocilizumab. On day 17, he presented with hypomimia, hypophonia, bradykinesia, cogwheel rigidity, shuffling gait, and micrographia, which was diagnosed as grade 2 IEC-HS. A brain FDG-PET scan showed hypometabolism of the bilateral frontal lobes; brain MRI was normal. He was diagnosed with stage IV ciltacabtagene autoleucel–associated parkinsonism.
His physicians tried treating him with intravenous gammaglobulin, methylprednisolone through day 67, anakinra for 7 days, and ruxolitinib twice daily. By day 50, the IEC-HS resolved, and the bradykinesia, cogwheel rigidity, shuffling gait, micrographia, and hypophonia improved by day 57. At day 165, ruxolitinib was lowered to 5 mg once daily without recurrence, and the patient resumed normal activities. He achieved a stringent complete remission, including measurable residual disease at day 100, which was sustained through 6 months.
Disclosure: For full disclosures of the study authors, visit jh.elmerpub.com.
