Ixazomib, lenalidomide, and dexamethasone is effective and well tolerated in multiply relapsed (≥2nd relapse) refractory myeloma: a multicenter real world UK experience.

There are limited real world data on ixazomib, lenalidomide, and dexamethasone (IRd) in multiply relapsed myeloma. We analyzed outcomes of 116 patients who received IRd predominantly at second and subsequent relapse including those refractory to proteasome inhibitors (PIs). With a median follow up 16.3 months, the overall response rate was 66.9%; median progression-free survival (PFS) was 17.7 months with median overall survival (OS) not reached (NR). PFS and OS were significantly shorter in advanced disease (PFS; 12.6 vs. 21.2 months (p = .01), OS; 15.9 months vs. NR (p = .01) for ISS3 vs. ISS 1&2, respectively). PFS and OS were significantly shorter in clinical high risk (CHR) compared to standard risk (SR) patients (PFS; 9.3 months vs. NR (p = .001), OS; 11.5 months vs. NR (p < .001), respectively). There was a trend toward shorter PFS in PI-refractory patients 13.7 vs. 19.6 months for non-PI refractory (p = .2). The triplet combination was generally well tolerated.

Real-world effectiveness and safety of ixazomib-lenalidomide-dexamethasone in relapsed/refractory multiple myeloma.

Real-world data on regimens for relapsed/refractory multiple myeloma (RRMM) represent an important component of therapeutic decision-making. This multi-centric, retrospective, observational study conducted by the treating physicians evaluated the effectiveness and safety of ixazomib-lenalidomide-dexamethasone (IRd) in 155 patients who received ixazomib via early access programs in Greece, the UK, and the Czech Republic. Median age was 68 years; 17% had an Eastern Cooperative Oncology Group performance status ≥ 2; median number of prior therapies was 1 (range 1-7); 91%, 47%, and 17% had received prior bortezomib, thalidomide, and lenalidomide, respectively. Median duration of exposure to ixazomib was 9.6 months. Overall response rate was 74%, including 35% very good partial response or better (16% complete response). Median progression-free survival (PFS) was 27.6 months (27.6 and 19.9 months in patients with 1 or > 1 prior lines, respectively). IRd treatment for ≥ 6 months was associated with longer PFS (hazard ratio 0.06). Fourteen patients (9%) discontinued IRd due to adverse events/toxicity in the absence of disease progression. Peripheral neuropathy was reported in 35% of patients (3% grades 3-4). These findings support the results of the phase III TOURMALINE-MM1 trial in a broader real-world RRMM population.

Pembrolizumab-induced autoimmune haemolytic anaemia and cholangitis.

Increasing numbers of patients are now offered immunotherapy as part of their cancer treatment. These treatments, while often very effective, have a wide range of adverse effects that are distinct from those of traditional chemotherapy regimens. Thyroid disease, dermatological disease, colitis and pneumonitis are some of the most commonly reported immune side effects. We present a case of life-threatening de novo autoimmune haemolytic anaemia (AIHA) complicated by immune cholangitis induced by pembrolizumab. An 81-year-old woman with metastatic melanoma completed a two-year course of pembrolizumab in August 2018 and six weeks later presented to hospital with jaundice. Admission haemoglobin (Hb) was 91 g/L, rapidly decreasing to 31 g/L, at which point she required admission to the intensive care unit. AIHA is a rare but potentially life-threatening complication of checkpoint inhibitors and should be considered in patients presenting with anaemia during or after immunotherapy treatment.

Bendamustine in combination with thalidomide and dexamethasone is a viable salvage option in myeloma relapsed and/or refractory to bortezomib and lenalidomide.

Treatment options are limited in myeloma relapsed or refractory to both bortezomib and lenalidomide (double-relapsed/refractory multiple myeloma; DRMM). Bendamustine is an antitumour agent that has efficacy in relapsed myeloma. We retrospectively analysed data from 30 DRMM patients who received a combination of bendamustine, thalidomide and dexamethasone (BTD) in 28-day treatment cycles. Bendamustine was administered with a cumulative dose of up to 200 mg/m(2). Thalidomide (50-150 mg) was given daily as tolerated, and dexamethasone was given at an equivalent dose of up to 160 mg per cycle. A median of 5 (2-9) treatment cycles were administered per patient. Twenty-six patients (87 %) achieved stable disease or better. At a median follow-up time of 12.1 (2.3-21.5) months, median (95 % CI) progression-free survival and overall survival were 4.0 (2.6-5.3) months and 7.2 (5.2-9.2) months, respectively. The most common grade 3-4 adverse events were haematological: anaemia (n = 8, 34.8 %), neutropenia (n = 16, 69.6 %) and thrombocytopenia (n = 10, 43.5 %). Non-haematological toxicities included pain (n = 3, 13.0 %), infection (n = 7, 30.4 %) and sensory neuropathy (n = 1, 4.3 %). We propose that BTD is a viable salvage treatment option for DRMM patients.