Key Points• Bendamustine-bortezomibdexamethasone is active and well tolerated in relapsed/ refractory myeloma.Bendamustine with bortezomib and dexamethasone was evaluated in 79 patients with relapsed/refractory multiple myeloma. Median age was 64 years, and patients had a median of 2 prior treatment lines (range, 1 to 6 lines). Bendamustine 70 mg/m 2 days 1 and 4; bortezomib 1.3 mg/m 2 intravenously days 1, 4, 8, and 11; and dexamethasone 20 mg days 1, 4, 8, and 11 once every 28 days was given for up to 8 cycles. Primary end point was overall response rate (ORR). Secondary end points were progression-free survival (PFS), overall survival, time to response, and toxicity. ORR was 60.8%, and when minor responses were included, 75.9%. Median time to response was 31 days. ORR rate was similar in patients previously exposed to bortezomib, lenalidomide, and bortezomib plus lenalidomide. PFS was 9.7 and OS was 25.6 months. Multivariate analysis showed high lactate dehydrogenase, ‡3 prior treatment lines, and low platelet counts correlating with short survival. Grade 3/4 thrombocytopenia was noted in 38%, and grade 3/4/5 infections were noted in 23%. Grade £2 polyneuropathy increased from 19% at baseline to 52% at cycle 8 and grade 4, from 0% to 7%. Bendamustine-bortezomib-dexamethasone is active and well tolerated in patients with relapsed/refractory myeloma. This trial was registered in the EudraCT database as -006421-13. (Blood. 2014 123(7):985-991)

Background. Chronic anemia is a common complication in patients with cancer, especially in those with advanced disease or who are under intensive chemotherapy. Because homologous blood transfusions involve some hazards, the safety and efficacy of recombinant human erythropoietin (r‐HuEPO) in the treatment of anemic patients with cancer with and without concomitant chemotherapy were studied. Methods. One‐hundred two cancer patients with hemoglobin less than 11 g/dl, ferritin greater than 30 μg/l, and creatinine < 220 μmol/l were enrolled in the study, 94 were eligible for efficacy evaluation. Sixty‐eight patients received chemotherapy (CT group) and 26 had no cytotoxic cancer treatment (NT group). Recombinant human erythropoietin was administered subcutaneously at a dose of 150 U/kg three times per week for 6 weeks; in nonresponders the dose was doubled for the subsequent 6 weeks. Response was defined as the achievement of a hemoglobin increase of 2 g/dl. Clinical and laboratory parameters, including serum erythropoietin (EPO) levels, performance status, and quality of life, were investigated at baseline and monitored at regular intervals thereafter. Results. Response was achieved by 52% and 62% of CT and NT patients, respectively. The highest response rates were observed in patients with lung cancer or with a histology of squamous cell carcinoma (both 80%). In responding patients, the symptoms of anemia subsided. They no longer needed blood transfusions after 4 weeks of therapy; and both their performance status and quality of life improved significantly. The NT patients achieved slightly more favorable results on lower weekly doses: 450 U/kg/week in NT versus 570 U/kg/week in CT patients. Serum EPO levels were higher in nonresponders at baseline and further increased during the course of treatment. Recombinant human erythropoietin was well tolerated by all patients. Conclusion. This multicenter study in a large patient collective shows that r‐HuEPO treatment represents a safe and effective means to increase the red cell mass and eliminate the need for blood transfusions in approximately 50% of the patients with chronic anemia of cancer. Responding patients not only have increased levels of hemoglobin, but their performance status also improves significantly, and they enjoy a significantly enhanced quality of life. Cancer 1995; 76:2319–29.

Background. Improvements in quality of life after treatment with recombinant human erythropoietin (rHuEPO) often have been reported in patients with endstage renal disease. In patients with chronic anemia of cancer, comparatively few systemic investigations have been performed. Methods. Various aspects of quality of life were selfreported on linear analogue scales of a slightly modified questionnaire that was first developed to assess toxicity of chemotherapy in patients with breast cancer. Thirty‐four patients with chronic anemia of cancer completed 10 items (feelings of well‐being, mood, level of activity, pain, nausea, appetite, physical ability, social activities, anxiety, and helpfulness of therapy) before and after 8 and 12 weeks of rHuEPO therapy. Results. Patients with response to the therapy significantly improved after 8 weeks of treatment in some items and after 12 weeks in all items. Patients with no response also had some improvement after 12 weeks of therapy. Hemoglobin levels correlated strongly with mood and appetite. World Health Organization (WHO) performance status improved significantly in patients with response but tended to diminish in those without. Median survival was 4.1 months in patients with no response and 12.0 months in those with response. After 12 weeks of therapy, the scores of the items “physical ability” and “social activities” proved to be significant prognostic factors, which surpassed the prognostic power of the WHO performance status. Conclusions. The results of rHuEPO therapy in chronic anemia of cancer are far more than cosmetics of laboratory values. They enable the patients with response to lead a physically and socially more active life with less anxiety, brighter moods, and an increased general feeling of well‐being.

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Chronic anemia of cancer can be corrected in approximately 50% of the cases by treatment with recombinant human erythropoietin (rHuEPO). Early prediction of responsiveness would avoid the emotional and financial burden of ineffective medical intervention. Eighty patients with chronic anemia of cancer undergoing treatment with rHuEPO (150 U/kg, 3 times per week by subcutaneous injection; after 6 weeks without response, 300 U/kg) participated in this study. Response was defined as a gain of at least 2 g/dL hemoglobin (Hb) within 12 weeks. Multivariate discriminant analysis and logistic regression analysis of response were performed on routine blood tests; serum levels of EPO, iron, ferritin, transferrin, and its receptor; World Health Organization (WHO) performance status; various cytokines; neopterin; stem cell factor; C- reactive protein; and alpha 1-antitrypsin. At baseline, none of these factors showed sufficient prognostic power. The following predictive algorithm was developed: (1) If after 2 weeks of therapy both the serum EPO level is > or = 100 mU/mL and Hb concentration has not increased by at least 0.5 g/dL, unresponsiveness of the patient is very likely (predictive power, 93%); otherwise, response may be predicted with an accuracy of 80%. (2) If both the serum level of EPO is less than 100 mU/mL and Hb concentration has increased by > or = 0.5 g/dL, response is highly probable (predictive power, 95%). (3) Alternatively, a serum ferritin level of > or = 400 ng/mL after 2 weeks of rHuEPO therapy strongly indicates unresponsiveness (predictive power, 88%), whereas a level less than 400 ng/mL suggests response in 3 of 4 patients.