Methods Pts were randomized 2:1 to ENZA 160 mg/d or PBO, stratified by baseline ECOG & mean Brief Pain Inventory score (BPI). Efficacy endpoints included Overall Survival (OS), radiographic progression-free survival (rPFS), & time to PSA progression (TTPP). In a post-hoc analysis, pts were evaluated by oral daily CS baseline use. Using a stepwise multivariate Cox proportional-hazards analysis, associations between the OS and the prespecified baseline factors ( treatment [Trt], age, region, ECOG, BPI, visceral disease, number of chemotherapy regimens, progression type at entry, LDH, PSA, hemoglobin, alkaline phosphatase) and CS use were evaluated.

Access through your institution Abstract We compared the physical and chemical properties of purported copies of recombinant human erythropoietin (rHuEPO) purchased from Korea, China, and India with the innovator product, Epoetin alfa, manufactured by Amgen Inc. All products were different from Epoetin alfa (Epogen®). The purported copies of rHuEPO from Korea, India, and China contained more glycoforms and other impurities.

In four others who received treatment, disease burden decreased by at least 30%. “What we've seen so far is impressive—durable responses and shrinking tumor masses in a cancer that's notoriously difficult to control,” says Roger Perlmutter, Amgen's executive vice president for R&D. Today's oncolytic virus immunotherapies aim for heightened therapeutic potency and tumor selectivity, says Mark Monane, a senior analyst with Needham & Company in New York. Among the 17 oncolytic virus therapies now in development, OncoVEX leads the pack, with phase 3 trials ongoing in both metastatic melanoma and head and neck cancer (Table 1 ). OncoVEX is an oncolytic herpes simplex type 1 virus (HSV-1) that has been enhanced to show greater selectivity for growth in transformed cells through deletions in ICP34.5 , which encodes a protein involved in preventing apoptosis, and by expressing US11 as an immediate-early, rather than late, gene.

Two novel agents with different mechanisms of action, selinexor5 and belantamab mafodotin,6 were recently approved for patients with relapsed or refractory MM (RRMM) who received ≥ 4 prior LOT but had overall response rates (ORRs) of only 21% to 34% in clinical trials.7 -9 Personalized immunotherapy using a chimeric antigen receptor (CAR) involves genetically modifying a patient's own T cells so that they can identify and kill malignant plasma cells.10 The first B-cell maturation antigen (BCMA)–directed CAR-T cell immunotherapy, idecabtagene vicleucel (ide-cel), was approved in the United States for patients with RRMM after exposure to ≥ 4 prior LOT11 and was granted conditional approval in 2021 in the European Union for patients with RRMM who received ≥ 3 therapies and progressed on their last therapy.12 Approval was based on the results from the phase II KarMMa trial, which demonstrated an ORR of 73% and a median progression-free survival (PFS) of 8.8 months across all dose cohorts in heavily pretreated patients (median six prior LOT).13 Ciltacabtagene autoleucel (cilta-cel, JNJ-68284528) is a differentiated CAR-T therapy with two BCMA-targeting single-domain antibodies to confer avidity.14 It was recently approved by the US Food and Drug Administration for the treatment of adult patients with RRMM after ≥ 4 prior LOT, including a PI, an IMiD, and an anti-CD38 monoclonal antibody.15 In March 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion of cilta-cel, for an indication in patients with ≥ 3 prior LOT.16 Initial results from the phase Ib/II, single-arm CARTITUDE-1 trial demonstrated that cilta-cel led to early, deep, and durable responses among 97 patients with RRMM exposed to a median of six prior therapies.14 At a median follow-up (MFU) of 12 months, ORR was 97% with 67% of patients reaching stringent complete response (sCR). The median duration of response (DOR) and median PFS were not estimable (NE).14 Here, we present a prespecified analysis of the CARTITUDE-1 study, which was completed in early 2022, with a MFU of 28 months. Subgroup analyses were conducted in the following patient subgroups: age ≥ 65 years, Black/African American, 3 and ≥ 4 prior LOT, triple-class refractory, penta-drug refractory, standard- and high-risk cytogenetic status, International Staging System (ISS) stage III, bone marrow plasma cell percentage at baseline (≤ 30%, > 30% to < 60%, and ≥ 60%), tumor BCMA expression at baseline (< 80%, ≥ 80%), and presence of plasmacytomas (bone-based and EM). RESULTS Section: Patients and Treatment As of the January 11, 2022, data cutoff, 66 of the 97 patients who received cilta-cel infusion remained on study (Fig 1 ). As previously reported, the median time from receipt of the apheresis material to release of cilta-cel was 29 days (interquartile range 28-33); no patient discontinued the study because of manufacturing failure.14 All patients treated with cilta-cel received a dose within the target range (median, 0.71 × 106 cells/kg; range, 0.51-0.95 × 106 ). At baseline, patients had received a median of six (range, 3-18) prior LOT.

Introduction Antibody-mediated pure red-cell aplasia is a rare syndrome of anemia associated with a low reticulocyte count, an absence of erythroblasts in the bone marrow, resistance to recombinant human erythropoietin (epoetin) therapy, and neutralizing antibodies against erythropoietin.1 Between 1988 and 1998, this syndrome was reported in three patients who had been treated with epoetin.2-4 By contrast, between 1998 and 2000, 13 patients with chronic kidney disease in France were found to have pure red-cell aplasia with neutralizing antierythropoietin antibodies after receiving epoetin administered subcutaneously1 ; 12 patients had received the Eprex formulation of epoetin alfa and 1 Neorecormon (a formulation of epoetin beta), both products that are marketed outside the United States.1 In response to the reports, the Food and Drug Administration (FDA) collected information on 82 patients worldwide, 78 of whom had received Eprex.5 In 2002, health authorities in France, Germany, Italy, Spain, and the United Kingdom concluded that the subcutaneous administration of Eprex should be considered contraindicated for treatment of anemia in patients with chronic kidney disease and mandated the intravenous administration of Eprex, which was thought to be less likely than subcutaneous administration to evoke an immune response.6-11 In contrast, health authorities in Canada and Australia encouraged, but did not require, intravenous administration.12,13 Health officials worldwide also recommended adherence to new storage and handling procedures for Eprex.6,14 In 2003, nine cases of antibody-associated pure red-cell aplasia were reported worldwide in patients who had received epoetin.14-19 In this article investigators from the Research on Adverse Drug Events and Reports group review the international experience with epoetin-associated pure red-cell aplasia.20 Methods The FDA's Adverse Event Reporting System receives adverse-event reports for epoetin alfa from drug-monitoring programs worldwide. Because the FDA does not receive adverse-event reports for epoetin beta, which is licensed outside the United States, adverse-event information for this same period for Neorecormon (Roche; also marketed as Recormon) was obtained from the manufacturer (Ruch R: personal communication).21 Estimates of the exposure-adjusted incidence of pure red-cell aplasia in the period from January 1, 2001, to December 31, 2003, were obtained from one of the manufacturers' Web sites, personal communications from the manufacturers of the three products, and a published survey.19,22 The case definition of epoetin-associated pure red-cell aplasia included the use of epoetin and a diagnosis consistent with the syndrome (pure red-cell aplasia, anemia, loss of efficacy of the epoetin product, and drug-specific antibodies). The data reviewed included the reporting date and country where pure red-cell aplasia was identified; the patient's age and sex; the cause of the anemia; and information related to the patient's chronic kidney disease, including the use or nonuse of dialysis, dates of initiation and discontinuation of the use of epoetin, the route of administration, dose, and schedule, and the features of the pure red-cell aplasia.

Nasopharyngeal or oropharyngeal tumor location, a cumulative radiation dosage > 5000 cGy, and the receipt of concomitant chemotherapy were found to increase the risk of OM in logistic regression models that controlled for patient age, gender, body weight, tumor stage, former or current alcohol or tobacco use, and type of radiation therapy (Table 3 ). The risk was lower for patients with advanced age (≥ 80 yrs). The risk of severe OM was found to be greatest for patients with nasopharyngeal tumors (adjusted OR of 10.1; 95% CI, 2.1–49.9), mean cumulative radiation dosages > 6500 cGy (OR of 10.4; 95% CI, 2.9–37.1), and concomitant chemotherapy (OR of 3.3; 95% CI, 1.4–8.0). Tumor location in the oral cavity (including the lip area) also was associated with a high risk of severe OM (OR of 6.2; 95% CI, 2.3–16.8). Patients with traditional indemnity insurance plans also were more likely to experience OM. When patients with any OM were compared with those without OM on a multivariate analysis, the former group were found to be approximately 4-fold more likely to have had unplanned breaks in radiation therapy (adjusted OR of 3.8; 95% CI, 1.7–8.5) and more than 3 times as likely to have been hospitalized (OR of 3.5; 95% CI, 1.3–9.5) (Table 5 ). They also were 3.4 times more likely to have had breaks or delays in chemotherapy, 6.1 times more likely to have had their dose of chemotherapy reduced, and nearly twice as likely to have received feeding tubes or TPN (for reasons other than prophylaxis) or indwelling i.v. lines, although all the corresponding 95% CIs overlapped 1.0.