Real world data on outcomes of anti-CD38 antibody treated, including triple class refractory, patients with multiple myeloma: a multi-institutional report from the Canadian Myeloma Research Group (CMRG) Database.

Multiple myeloma (MM) remains incurable despite the availability of novel agents. This multi-center retrospective cohort study used the Canadian Myeloma Research Group Database to describe real-world outcomes of patients withanti-CD38 monoclonal antibody (mAb) refractory MM subsequently treated with standard of care (SoC) regimens. Patients with triple class refractory (TCR) disease (refractory to a proteasome inhibitor, immunomodulatory drug, and anti-CD38 mAb) were examined as a distinct cohort. Overall, 663 patients had disease progression on anti-CD38 mAb therapy, 466 received further treatment (346 with SoC regimens were included, 120 with investigational agents on clinical trial and were excluded). The median age at initiation of subsequent SoC therapy of 67.9 (range 39.6-89.6) years with a median of 3 prior lines (range 1-9). The median PFS and OS from the start of subsequent therapy was 4.6 (95% CI 4.1-5.6) months and 13.3 (95% CI 10.6-16.6) months, respectively. The median PFS and OS of patients with TCR disease (n = 199) was 4.4 (95% CI 3.6-5.3) months and 10.5 (95% CI 8.5-13.8) months. Our results reinforce that real-world patients with relapsed MM, particularly those with TCR disease, have dismal outcomes. There remains an urgent unmet need for the development of and access to effective therapeutics for these patients.

Aplastic anemia secondary to nivolumab and ipilimumab in a patient with metastatic melanoma: a case report.

BACKGROUND: Immune checkpoint blockade (ICB) is becoming an increasingly prevalent strategy in the clinical realm of cancer therapeutics. With more patients being administered ICB for a host of tumor types, the scope of adverse events associated with these drugs will likely grow. Here we report a case of aplastic anemia (AA) in a patient with metastatic melanoma secondary to dual ICB therapy. To our knowledge, this is only the second case of AA secondary to dual ICB in the literature, and the first to have a positive patient outcome. CASE PRESENTATION: A 51-year old male with metastatic melanoma was started on dual immune checkpoint blockade, in the form ipilimumab (3 mg/kg) and nivolumab (1 mg/kg). Two weeks following the second cycle, he presented to the emergency department with profound polypipsia, polyuria and fatigue. The patient was diagnosed with diabetic ketoacidosis secondary to immune therapy induced type-1 diabetes and was admitted to the ICU. While in hospital the patient developed a symptomatic anemia and neutropenia. A bone marrow biopsy revealed a markedly hypocellular marrow with trinlineage hypoplasia with no evidence of myelodysplasia, neoplasm or excess blasts. Flow cytometry revealed an inverted CD4+:CD8+ ratio and an absence of hematogones. Taken together the presumed etiology was AA secondary to immunotherapy. The patient was subsequently started in IV methylprednisone 70 mg/day for 8 days, followed by a prednisone taper. This intervention rectified the bicytopenia and to date the patient has shown stable blood counts. CONCLUSION: With the use of ICBs becoming increasingly prevalent in the clinical arena, the number of patients presenting with immune-related adverse events will likely increase. The current case illustrates the need to be vigilant when managing cancer patients receiving ICB. The resolution of this patient's AA with corticosteroids highlights the value of early detection and appropriate treatment of these rare immune-mediated adverse events.

CyBorD induction therapy in clinical practice.

Cyclophosphamide, bortezomib and dexamethasone (CyBorD) is a highly active three-drug induction regimen for untreated transplant-eligible multiple myeloma patients. Although CyBorD has been evaluated only in the phase 2 setting in a limited number of patients, its high efficacy and ease of administration have led to its widespread use. Given that clinical trial efficacy can overestimate real-life effectiveness, we reviewed our institutional experience with 109 newly diagnosed patients who were treated with CyBorD in a non-clinical trial setting. After a median of four cycles, overall response rate (ORR) and very good partial response rate or better (⩾VGPR) were 95 and 66%, respectively, comparable to phase 2 studies of CyBorD and other three/four-drug induction regimens. All patients subsequently underwent successful stem cell collection and upgraded responses to ORR 98% and ⩾VGPR 79% post transplant. At a median follow-up of 19.8 months after diagnosis, the 2-year OS probability was 95.3% (95%CI: 89-98). The presence of concurrent plasmacytoma at diagnosis was the only prognostic factor predicting poorer survival (HR=5.56; 95%CI: 0.92-33.74; P=0.03). CyBorD was well-tolerated, with no severe peripheral neuropathy and minimal hematologic toxicity. Therefore, CyBorD is a convenient, well-tolerated, highly effective induction regimen in preparation for autologous SCT in real-life clinical practice.

Early relapse after single auto-SCT for multiple myeloma is a major predictor of survival in the era of novel agents.

The role of auto-SCT in the treatment of multiple myeloma (MM) in the era of novel agents continues to evolve. It is now clear that the depth of response and clinical outcomes have significantly improved as a result of the combination of these strategies. However, not all patients with MM who undergo auto-SCT are able to sustain a meaningful response and 20% of patients relapse shortly after auto-SCT. In this study, we aimed to assess the impact of early relapse (ER) after auto-SCT on OS for MM patients undergoing single auto-SCT who had received novel agent-based induction regimens. All consecutive patients with MM undergoing single auto-SCT from January 2002 to September 2012 who had novel induction therapy were evaluated. A total of 184 patients were identified. The median OS and PFS for the group of transplanted patients were 93 and 25.4 months, respectively. Median time to relapse was 17.2 months with 40% having relapsed at the time of analysis. ER (<12 months post auto-SCT) was seen in 27 (36%) out of 75 patients who had relapsed, and median OS was significantly shorter than in those with non-ER. Multivariate analysis showed ER as the major independent prognostic factor for OS. On the basis of these findings, we conclude that not only attainment of a good response, but sustainability of it, appears to be a major prognostic variable in MM in the era of novel therapy. Patients with ER post auto-SCT should biologically be characterized in prospective studies to better understand the mechanisms of resistance associated with this particular entity.

Light chain deposition disease: novel biological insights and treatment advances.

Light chain deposition disease (LCDD) is a monoclonal gammopathy characterized by nonamyloid deposition of immunoglobulin light chains in various organs. Most cases present with renal dysfunction, a ubiquitous feature of this disease, and in some instances, it may progress to end-stage renal disease. Unfortunately, until now, no standard treatment has been established. The use of alkylating agents and steroids has been extensively reported. However, conventional chemotherapy response is generally limited with minor effects on kidney function. The use of novel agents such as bortezomib has shown a more rapid response with a dramatically important reduction of light chains in serum and/or urine in small series of cases. Furthermore, autologous stem cell transplantation has been reported as a feasible strategy in LCDD, able to prolong the dialysis-free survival. Nonetheless, toxicity from these therapies should be considered carefully because most of patients might present with kidney dysfunction that could limit the use of some agents.

[Non-Hodgkin's lymphoma: biologic classification, diagnosis and treatment]. / Linfoma no Hodgkin: clasificación biológica, diagnóstico y tratamiento.

The lymphomas are the seventh most common causes of death from cancer in the United States. There is a steady increase in the incidence of non-Hodgkin's Lymphoma from childhood through the age 80, and in the United States, is more common in males than in females. The etiology of the lymphomas is unknown. Molecular biology techniques have allowed the elucidation of many cellular function involved in tumorigenesis. Clinical presentation of non-Hodgkin's lymphoma are varied, and depend on the histologic subtype, the extent (or stage) of the disease, and the primary site of the tumor, most often present lymph node disease, children typically have extranodal disease involving the mediastinum, abdomen or head and neck. Non-Hodgkin's lymphoma are categorized as low, intermediate, or high grade, on the basis of their clinical aggressiveness. Low and intermediate grade tumors predominate in adults, whereas more than 90 percent of children with non Hodgkin's lymphoma have a high grade tumor. The field of cancer therapy has progressed rapidly. In the most recent era, treatment has included multiagent chemotherapy directed to the stage and histologic subtype of the disease. Gene therapy has now become a standard experimental approach for treating cancer were conventional therapies have failed.