John Maciejewski

Clinical and Safety Profile of High-Dose Interleukin-2 Treatment in Elderly Patients with Metastatic Melanoma and Renal Cell Carcinoma

Objective: High-dose interleukin-2 (IL-2) is effective immunotherapy for the treatment of metastatic melanoma and renal cell carcinoma (RCC) but has been contraindicated in elderly patients. This study assessed the safety and therapeutic efficacy of high-dose IL-2 in patients ≥65 years of age with metastatic melanoma and RCC. Methods: A prospectively collected clinical database of 104 consecutive melanoma or RCC patients treated with high-dose IL-2 between 2009 and 2012 was used to compare clinical outcomes and adverse events in patients ≥65 years of age with those of younger patients. Results: There were 22 (21%) patients ≥65 years and 82 (79%) patients <65 years of age. The mean number of IL-2 doses was lower in older patients during cycle 1 of treatment (7.2 vs. 8.6, p = 0.012). There were no other differences in dosing pattern by age group. There was a higher rate of selected cardiac, constitutional, hematologic, metabolic and renal toxicities in younger patients (p < 0.05). Overall, objective responses and survival were not affected by age, though older patients had a higher partial response rate (p = 0.04). Conclusions: IL-2 is safe and has comparable therapeutic effectiveness in patients ≥65 years. Age should not be considered a contraindication to treatment with IL-2 in otherwise eligible patients.

Posttraumatic stress symptoms predict impaired neutrophil recovery in stem cell transplant recipients

Despite the potentially life‐saving effects of stem cell transplant (SCT), many transplant patients experience traumatic stress reactions due to mortality threat, interpersonal isolation, financial and occupational loss, and invasive medical procedures. Emerging evidence suggests that trauma‐related stress symptoms (TSS) predict significant health complications following SCT. The aim of the current prospective study was to examine TSS in the acute aftermath of SCT as a predictor of neutrophil recovery following SCT, a crucial component of immune defense against infection.

Incident hyperglycemia, parenteral nutrition administration and adverse outcomes in patients with myeloma admitted for initial auto-SCT

Parenteral nutrition (PN) exacerbates hyperglycemia, which is associated with increased morbidity and mortality in various cancer populations. By using a retrospective design, we examined incident hyperglycemia in PN and non-PN recipients and the associations with clinical events and 5-year survival in a cohort treated for myeloma with melphalan and auto-SCT (n=112). Clinical comparisons were made at admission, and ‘before’ and ‘after’ initiating PN to discern differences and temporality. Actual infusion times were used for PN patients; time frames based on mean PN infusion days were created for the non-PN recipients. Oral intake was lower ‘before’ in PN vs non-PN patients (P<0.001); however, no differences in mucositis, emesis, infections or transfusions were detected ‘before.’ Incident hyperglycemia (⩾7.0 mmol/L) was significant ‘after’ PN initiation, and PN recipients experienced delays in WBC (P<0.05) and platelet engraftment (P=0.009), and required significantly greater RBC (P=0.0014) and platelet (P=0.001) support ‘after’ than non-PN patients. Neutropenic fever and longer hospital stay were more frequent among PN vs non-PN recipients (P<0.001). Differences in 5-year mortality were not apparent. The findings fail to support clinical benefits of PN administration during auto-SCT for myeloma. Further study is needed to discern if hyperglycemia or feeding per se was deleterious in this patient population.

Induction chemotherapy before autologous stem cell transplantation for symptomatic plasma cell myeloma – does it matter?

Autologous stem cell transplantation is the preferred treatment option for younger patients with symptomatic plasma cell myeloma. Most patients with newly diagnosed plasma cell myeloma receive 3–4 cycles of induction chemotherapy to achieve a level of disease control before proceeding to stem cell transplant. The ideal induction regimen for transplant-eligible patients shall allow more patients to proceed with transplant, rapidly and effectively control the disease, reverse disease-related complications, avoid early death, and is associated with minimal acute and long-term toxicities. Because of the concerns of potential damages to hematopoietic stem cells, alkylating agent regimens, specifically melphalan, are usually avoided for induction in transplant-eligible patients. Before the advance of immunomodulatory agents (IMiD) and proteasome inhibitors, the combination of vincristine, adriamycin, and dexamethasone (VAD) and variants were the most commonly used induction regimens. Recent reports as discussed in this review suggests that VAD is no longer the induction chemotherapy of choice for transplant eligible patients. Newer regimens incorporating IMiD and/or proteasome inhibitor into the induction regimen improve response rates and progression-free survival before and after the transplant and are evolving as the treatment of choice. Here, we review the available data on these newer induction regimens and to evaluate the potential impacts on the patient outcomes.