FDA Approval Summary: Ciltacabtagene Autoleucel for Relapsed or Refractory Multiple Myeloma.

In February 2022, the FDA approved ciltacabtagene autoleucel, a chimeric antigen receptor (CAR) T-cell therapy targeting the B-cell maturation antigen, for adult patients with relapsed/refractory multiple myeloma after ≥4 lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Approval was based on overall response rate (ORR), complete response (CR) rate, and duration of response (DoR) in 97 adult patients in a single-arm, open-label, multicenter phase 2 trial (CARTITUDE-1 [NCT03548207]). Patients received a single infusion of ciltacabtagene autoleucel, preceded by lymphodepleting chemotherapy. Of the 97 patients evaluable, ORR was 97.9% [95% confidence interval (CI), 92.7-99.7] with a stringent CR rate of 78.4% (95% CI, 68.8-86.1). After median follow-up of 18 months, the median DoR was 21.8 months (95% CI, 21.8-not estimable [NE]) in responders (PR or better) and NE (95% CI, 21.8 months-NE) in patients who achieved stringent CR. Serious adverse reactions occurred in 55% of the 97 patients evaluated for safety. Grade 3 or higher cytokine release syndrome (CRS) and neurologic toxicities occurred in 5% and 11% of the patients, respectively, leading to a Risk Evaluation and Mitigation Strategy. Neurologic toxicities included immune effector cell-associated neurologic syndrome, typically seen with CAR-T products, parkinsonism, peripheral neuropathy, cranial nerve palsies, and Guillain-Barré syndrome. One fatal case of hemophagocytic lymphohistiocytosis/macrophage activation syndrome occurred. Prolonged and recurrent grade 3 or 4 cytopenias occurred; a single patient required hematopoietic stem-cell rescue.

Bilateral nonpitting edema and xerotic skin.

When treatment for cellulitis and a suspected exacerbation of congestive heart failure failed, we ordered a biopsy. The pathology report made the diagnosis clear.

Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts.

BACKGROUND: Ruxolitinib, a Janus kinase 1 and 2 inhibitor, demonstrated improvements in spleen volume, symptoms, and survival over placebo and best available therapy in intermediate-2 or high-risk myelofibrosis patients with baseline platelet counts ≥100 × 109/L in phase III studies. The most common adverse events were dose-dependent anemia and thrombocytopenia, which were anticipated because thrombopoietin and erythropoietin signal through JAK2. These events were manageable, rarely leading to treatment discontinuation. Because approximately one-quarter of MF patients have platelet counts <100 × 109/L consequent to their disease, ruxolitinib was evaluated in this subset of patients using lower initial doses. Interim results of a phase II study of ruxolitinib in myelofibrosis patients with baseline platelet counts of 50-100 × 109/L are reported. METHODS: Ruxolitinib was initiated at a dose of 5 mg twice daily (BID), and doses could be increased by 5 mg once daily every 4 weeks to 10 mg BID if platelet counts remained adequate. Additional dosage increases required evidence of suboptimal efficacy. Assessments included measurement of spleen volume by MRI, MF symptoms by MF Symptom Assessment Form v2.0 Total Symptom Score [TSS]), Patient Global Impression of Change (PGIC); EORTC QLQ-C30, and safety/tolerability. RESULTS: By week 24, 62% of patients achieved stable doses ≥10 mg BID. Median reductions in spleen volume and TSS were 24.2% and 43.8%, respectively. Thrombocytopenia necessitating dose reductions and dose interruptions occurred in 12 and 8 patients, respectively, and occurred mainly in patients with baseline platelet counts ≤75 × 109/L. Seven patients experienced platelet count increases ≥15 × 109/L. Mean hemoglobin levels remained stable over the treatment period. Two patients discontinued for adverse events: 1 for grade 4 retroperitoneal hemorrhage secondary to multiple and suspected pre-existing renal artery aneurysms and 1 for grade 4 thrombocytopenia. CONCLUSIONS: Results suggest that a low starting dose of ruxolitinib with escalation to 10 mg BID may be appropriate in myelofibrosis patients with low platelet counts.