Advances in the Treatment of Relapsed and Refractory Multiple Myeloma in Patients with Renal Insufficiency: Novel Agents, Immunotherapies and Beyond.

BACKGROUND: Renal insufficiency is one of the most frequent complications in multiple myeloma. The incidence of renal insufficiency in patients with multiple myeloma ranges from 20% to 50%. Renal impairment in patients with multiple myeloma results primarily from the toxic effects of monoclonal light chains on the kidneys. Dehydration, hypercalcemia, hyperuricemia, the application of nephrotoxic NSARs, antibiotics, contrast agents, etc., all play a major role in the deterioration of renal function in patients with multiple myeloma. The diagnosis and treatment of these patients use an interdisciplinary approach in consultation with hematologist-oncologists, radiologists, nephrologists and intensive care specialists. Using new drugs in the treatment of patients with refractory/relapsed multiple myeloma and renal insufficiency markedly improves progression-free survival and overall survival in these patients. CONCLUSIONS: New drugs have helped to widen the treatment options available for patients with renal impairment and refractory/relapsed multiple myeloma, since dose adjustments are unnecessary with carfilzomib as well as with panobinostat, elotuzumab, pomalidomide or daratumumab in patients with renal impairment. Several new substances for the treatment of refractory/relapsed multiple myeloma have been approved in the meantime, including belantamab mafodotin, selinexor, melflufen, venetoclax, CAR T-cell therapy and checkpoint inhibitors. Ongoing studies are investigating their administration in patients with renal impairment.

Perforating folliculitis, angioedema, hand-foot syndrome--multiple cutaneous side effects in a patient treated with sorafenib.

A patient with clear cell renal cell carcinoma was treated with sorafenib, a multikinase inhibitor, which induced a variety of cutaneous side effects. In addition to xerosis, he developed angioedema (AE), hand-foot syndrome (HFS) and perforating folliculitis (PF). The latter three occurred in a dose-dependent manner. AE was observed at the recommended daily dose of 800 mg. Dose reduction to 400 mg prevented its recurrence. At this dose level, the patient exhibited HFS, which cleared upon further reduction of the dose. While receiving 200 mg, the patient developed PF. To the best of our knowledge, this is the first description of a case of PF during treatment with sorafenib.

Routine clinical use of alemtuzumab in patients with heavily pretreated B-cell chronic lymphocytic leukemia: a nation-wide retrospective study in Austria.

BACKGROUND: In previous studies, alemtuzumab demonstrated considerable activity in patients with previously treated B-cell chronic lymphocytic leukemia (CLL), including fludarabine-refractory disease. In this retrospective study, the authors evaluated the benefit of alemtuzumab monotherapy in unselected patients with advanced, previously treated CLL who received treatment in the routine clinical setting. METHODS: Data were collected from 115 consecutive patients who received alemtuzumab therapy at 25 participating centers in Austria. Patients received a median of 3 prior lines of therapy (range, 1-11 prior lines of therapy), and 59% had fludarabine-refractory disease. Alemtuzumab was administered intravenously or subcutaneously with a planned schedule of 30 mg 3 times per week for up to 12 weeks. Patients received valacyclovir and trimethoprim/sulfamethoxazole for antiinfective prophylaxis. RESULTS: The overall response rate was 23%, with complete responses achieved in 5% of patients. Stable disease (SD) was achieved in 36% of patients. After a median follow-up of 17.5 months, the median overall survival (OS) was 20.2 months for all patients. A multivariate Cox regression analysis that included pretreatment baseline characteristics, response to therapy, and cumulative dose of alemtuzumab indicated that bulky lymphadenopathy, the administration of > r =3 previous therapies, and lack of response to alemtuzumab remained significant independent risk factors for inferior OS. The median OS had not been reached for responding patients. The median OS was 29.5 months for patients with SD and 10.8 months for patients with progressive disease. CONCLUSIONS: The broad use of alemtuzumab in the routine clinical practice setting is feasible and active in unselected patients with pretreated CLL, and the current results confirmed the activity and safety of this agent, as reported in previously published clinical studies.

A rare case of interstitial pneumonitis after tandem high-dose melphalan conditioning and autologous stem cell transplantation in multiple myeloma.

A 57-yr-old woman with multiple myeloma received an autologous tandem transplant at a 4-month interval. She was conditioned twice with 225 mg/m2 melphalan. After the second transplant, interstitial pneumonitis (IP) ensued. The clinical course was life threatening and mechanical ventilation was required for 32 d. All attempts to identify an infectious agent failed. A presumptive diagnosis of idiopathic IP, possibly related to melphalan toxicity, was made. High-dose methylprednisolone administration led to rapid and durable improvement. Melphalan was employed for conditioning in the tandem setting with an interval of only 3-4 months between two courses or a dose elevation to 225 instead of 200 mg/m2, may have induced IP which responded favorably to methylprednisolone.