Comorbidities portend a poor prognosis among patients with CLL treated with ibrutinib. Prospective studies are needed to optimize the treatment of patients with CLL who have comorbidities. Cancer 2018. © 2018 American Cancer Society.

†Spirometry results were expressed as percentage of predicted based on recently published all-age/multiethnic reference equations using the fifth percentile as the lower limit of normal (LLN) for the set of equations derived for black individuals (Aggarwal and Agarwal 2007). † †Obstructive spirometry patterns were defined as a FEV1/ FVC ratio below LLN. Ibrutinib is an effective treatment of autoimmune haemolytic anaemia in chronic lymphocytic leukaemiaAutoimmune haemolytic anaemia (AIHA) is a life-threatening complication of chronic lymphocytic leukaemia (CLL). It is the most common variant of autoimmune cytopenia in CLL, with an incidence of~2Á3% as reported in a recent retrospective analysis of 1750 patients (Zent et al, 2009). AIHA most commonly develops after CLL diagnosis, but may be the presenting feature in a minority of patients. AIHA in CLL typically results from production of 'warm' immunoglobulin G (IgG) type antibodies (directed against red blood cells) by the non-malignant B-cells (Hamblin et al, 1986). Furthermore, monoclonal CLL cell-derived IgM antibodies were also implicated in autoimmunity (Broker et al, 1988), but cases of IgM-mediated AIHA in CLL are extremely infrequent. AIHA in CLL is treated with prednisone at 1 mg/kg for 2-4 weeks, followed by slow taper over 2-3 months (Hamblin, 2006;Visco et al, 2014). While generally safe, this therapy is associated with significant side effects in older patients, which represent the majority of patients with CLL. Furthermore, refractoriness to steroid therapy as well as necessity to administer high maintenance doses of prednisone to achieve adequate haemoglobin levels establish a need for further therapy. Single agent rituximab, splenectomy, ciclosporin and chemotherapy regimens (cyclophosphamide, vincristine, prednisone) have shown efficacy (Bowen et al, 2010;Visco et al, 2014). Recently, inhibitors of B-cell receptor-associated kinases have been introduced into clinical practice (Awan & Byrd, 2014). A Bruton tyrosine kinase inhibitor, ibrutinib, has been approved for therapy of relapsed/refractory CLL and upfront therapy of CLL with del (17p). However, clinical trials involving this agent excluded patients with uncontrolled haemolysis. Here we report a case of a patient with CLL with del (17p) presenting with AIHA in whom control of a haemolytic process was achieved with ibrutinib.A 70-year-old man was diagnosed with asymptomatic CLL, Rai stage 0. At the time of diagnosis, his white blood cell count (WBC) was 38Á2 9 10 9 /l with 80% lymphocytes, haemoglobin 122 g/l and a platelet count of 162 9 10 9 /l. Peripheral blood immunophenotyping demonstrated a population of CD5/CD19 positive, CD20-dim j-restricted B-cells that were CD38-negative and ZAP70-negative. The patient was lost to follow-up and 12 months later presented Haematology, 2015, 170, 727-736 with complaints of fatigue, generalized weakness, dyspnea and chest pain on mild exertion. A complete blood count showed a WBC of 72Á6 9 10 9 /l with 80% lymphocytes, haemoglobin 68 g/l and a plat...

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Background Melphalan flufenamide (melflufen), an alkylating peptide-drug conjugate, plus dexamethasone showed clinical activity and manageable safety in the phase 2 HORIZON study. We aimed to determine whether melflufen plus dexamethasone would provide a progression-free survival benefit compared with pomalidomide plus dexamethasone in patients with previously treated multiple myeloma. MethodsIn this randomised, open-label, head-to-head, phase 3 study (OCEAN), adult patients (aged ≥18 years) were recruited from 108 university hospitals, specialist hospitals, and community-based centres in 21 countries across Europe, North America, and Asia. Eligible patients had an ECOG performance status of 0-2; must have had relapsed or refractory multiple myeloma, refractory to lenalidomide (within 18 months of randomisation) and to the last line of therapy; and have received two to four previous lines of therapy (including lenalidomide and a proteasome inhibitor). Patients were randomly assigned (1:1), stratified by age, number of previous lines of therapy, and International Staging System score, to either 28-day cycles of melflufen and dexamethasone (melflufen group) or pomalidomide and dexamethasone (pomalidomide group). All patients received dexamethasone 40 mg orally on days 1, 8, 15, and 22 of each cycle. In the melflufen group, patients received melflufen 40 mg intravenously over 30 min on day 1 of each cycle and in the pomalidomide group, patients received pomalidomide 4 mg orally daily on days 1 to 21 of each cycle. The primary endpoint was progression-free survival assessed by an independent review committee in the intention-to-treat (ITT) population. Safety was assessed in patients who received at least one dose of study medication. This study is registered with ClinicalTrials.gov, NCT03151811, and is ongoing. Findings Between June 12, 2017, and Sept 3, 2020, 246 patients were randomly assigned to the melflufen group (median age 68 years [IQR 60-72]; 107 [43%] were female) and 249 to the pomalidomide group (median age 68 years [IQR 61-72]; 109 [44%] were female). 474 patients received at least one dose of study drug (melflufen group n=228; pomalidomide group n=246; safety population). Data cutoff was Feb 3, 2021. Median progression-free survival was 6•8 months (95% CI 5•0-8•5; 165 [67%] of 246 patients had an event) in the melflufen group and 4•9 months (4•2-5•7; 190 [76%] of 249 patients had an event) in the pomalidomide group (hazard ratio [HR] 0•79, [95% CI 0•64-0•98]; p=0•032), at a median follow-up of 15•5 months (IQR 9•4-22•8) in the melflufen group and 16•3 months (10•1-23•2) in the pomalidomide group. Median overall survival was 19•8 months (95% CI 15•1-25•6) at a median follow-up of 19•8 months (IQR 12•0-25•0) in the melflufen group and 25•0 months (95% CI 18•1-31•9) in the pomalidomide group at a median follow-up of 18•6 months (IQR 11•8-23•7; HR 1•10 [95% CI 0•85-1•44]; p=0•47). The most common grade 3 or 4 treatment-emergent adverse events were thrombocytopenia (143 [63%] of 228 in the melflufen group vs...

Although long-term proteasome inhibitor therapy improves outcomes in multiple myeloma, many patients cannot tolerate long-term treatment or might require or prefer to continue treatment outside the hospital or clinic. The US MM-6 study is evaluating the in-class transition from parenteral bortezomib-to oral ixazomibbased therapy in routine clinical practice. Preliminary results indicate feasibility, prolonged therapy duration, promising efficacy, and treatment adherence and satisfaction. Background: The ongoing US MM-6 study is investigating in-class transition (iCT) from parenteral bortezomibbased induction to all-oral IRd (ixazomib-lenalidomide-dexamethasone) with the aim of increasing proteasome inhibitor (PI)-based treatment adherence and duration while maintaining patients' health-related quality of life (HRQoL) and improving outcomes. Patients and Methods: US community sites are enrolling nonetransplanteligible patients with newly diagnosed multiple myeloma (MM) with no evidence of progressive disease after 3 cycles of bortezomib-based therapy to receive IRd (up to 39 cycles or until progression or toxicity). The patients use mobile or wearable digital devices to collect actigraphy (activity and sleep) data and electronically complete HRQoL, treatment satisfaction and medication adherence questionnaires. The primary endpoint is progressionfree survival. The key secondary endpoints include response rates and therapy duration. Results: At the data cutoff, 84 patients had been treated (median age 73 years; 44% aged ! 75 years; 49% men; 15% Black or African American; and 10% Hispanic or Latino). Of the 84 patients, 62% were continuing therapy. The mean duration of total PI therapy was 10.1 months and for the IRd regimen was 7.3 months. With an 8-month median follow-up, the 12-month progression-free survival rate was 86% (95% confidence interval, 73%-93%) from both the start of bortezomib-based treatment and the start of IRd. The overall response rate was 62% (complete response, 4%; very good partial response, 25%; partial response, 33%) after bortezomib-based induction and 70% (complete response, 26%; very good partial response, 29%; partial response, 15%) after iCT. The IRd safety profile was consistent with previous clinical trial data, and HRQoL and treatment satisfaction were maintained. Conclusion: