When incorporated into high-dose therapy for myeloma, thalidomide increased the frequency of complete responses and extended event-free survival at the expense of added adverse effects without improving overall survival. (ClinicalTrials.gov number, NCT00083551.).

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Summary A group of 256 newly diagnosed myeloma patients were enrolled in a phase III study that included 4 monthly cycles of induction chemotherapy and tandem transplant. All patients were randomized to either receive or not receive thalidomide. A total of 221 patients (86%) received no prophylactic anticoagulation (cohort I); 35 patients received low dose coumadin (cohort II). The incidence of deep vein thrombosis (DVT) was significantly higher in the thalidomide arm hazard ratio: 4·5; P < 0·0001). As low dose coumadin (1 mg/d) failed to decrease thrombotic complications in 35 patients (cohort II), low molecular weight heparin (LMWH, enoxaparin 40 mg s.c. q.d.) was instituted as DVT prophylaxis in the thalidomide‐treated patients (n = 68) of the subsequent cohort (n = 130, cohort III). This intervention eliminated the difference in DVT incidence between the two arms (thalidomide and no thalidomide). Within cohorts I and II, 36 patients, in whom thalidomide was discontinued after experiencing a thrombotic episode during chemotherapy, subsequently resumed the drug on full anticoagulation; with a median follow‐up of 22 months, DVT recurred in four patients (11%). After completing induction and tandem transplantation, 55 patients were re‐exposed to thalidomide and chemotherapy during consolidation treatment. Thrombotic complications were observed in 4%. Our experience, although not based on a randomized study, suggests that the excess frequency of thrombosis in patients treated with chemotherapy and thalidomide can be safely reduced by the prophylactic use of LMWH. The rate of DVT recurrence observed in our study upon thalidomide resumption was sufficiently low to allow its continuation in patients who may benefit from this therapeutic intervention.

Summary:To evaluate the role of high-dose melphalan and autologous transplant (AT) in reversing dialysis-dependent renal failure, 59 patients still on dialysis at the time of AT were analyzed. A total of 37 patients had been on dialysis p6 months. A 5-year event-free and overall survival rate of all patients after AT was 24 and 36%, respectively. Of 54 patients evaluable for renal function improvement, 13 (24%) became dialysis independent at a median of 4 months after AT (range: 1-16). Dialysis duration p6 months prior to first AT and pre-transplant creatinine clearance 410 ml/min were significant for renal function recovery: 12 of 36 (33%) p6 months vs one of 18 patients (6%) 46 months on dialysis recovered renal function; 10 of 26 (38%) with 410 ml/min vs three of 28 (11%) with p10 ml/min of creatinine clearance (both Po0.05). Quality of response after autotransplant was also significant: 12 of 31 (39%) being greater than partial remission after AT vs one of 21 patients (5%) attaining partial remission or less became independent of dialysis (Po0.05). Our data suggest that significant renal failure can be reversible and AT should be considered early in the disease course. Renal insufficiency is not uncommon in patients with myeloma, with a 30% incidence at initial presentation increasing further as the disease progresses. 1 Patients who require dialysis are known to have a poor prognosis, 2 although myeloma has been known to be one of the reversible causes of the end-stage renal disease. 3 Several studies have shown equivalent response rates to chemotherapy in myeloma patients with mild to moderate renal insufficiency, compared with those who have normal renal function, and response is frequently associated with gradual improvement in creatinine clearance. Recovery from renal insufficiency appears to depend on the underlying cause of the kidney failure. 2 Complete recovery was observed only in the absence of global tubular atrophy and interstitial damage, whereas cast-induced tubular obstruction by Tamm-Horsfall protein did not seem to influence the outcome. 4 Partial improvement in patients with light-chain nephropathy, characterized as diffuse mesangial nodular lesion and tubulointerstitial changes, has been reported only occasionally, suggesting a possibility of response presumably related to the degree of involvement. 5,6 Similar observations were made in patients with amyloid involvement of kidneys, especially after high-dose therapy and autotransplant. 7 We have previously reported on the outstanding outcome of 81 patients with renal failure after high-dose melphalan and autotransplant, including 38 patients on dialysis at the time of first autotransplant. 8 Of these, 21 and 31 patients achieved complete remission (CR) after the first and second autotransplant, respectively, with 48% eventfree and 55% overall survival probabilities at 3 years. On further follow-up of patients on dialysis, we have witnessed slow but persistent improvement in renal function in a limited number of patients to the extent that...

There is a growing body of evidence supporting the synergistic roles of radiotherapy and immunotherapy in the treatment of malignancy. Published case studies of the abscopal effect have been reported with the use of ipilimumab and radiotherapy in metastatic melanoma, but evidence supporting the routine use of this combination of therapy is limited. We conducted a retrospective analysis to evaluate patients treated with ipilimumab for advanced melanoma at a single institution from May 2011 to June 2015. Patients were grouped into those who had received concurrent radiotherapy while on ipilimumab (Ipi-RT), and those who did not. We then evaluated the treatment response following completion of ipilimumab. A total of 101 patients received ipilimumab in the prespecified time frame. 70 received Ipi-RT and 31 received ipilimumab without concurrent radiotherapy. Median overall survival (OS) was significantly increased in the concurrent Ipi-RT arm at 19 months vs. 10 months for ipilimumab alone (p = 0.01). Median progression free survival (PFS) was marginally increased in the Ipi-RT group compare with the ipilimumab alone group (5 months vs. 3 months, p = 0.20). Rates of complete response (CR) were significantly increased in the Ipi-RT group vs. ipilimumab alone (25.7% vs. 6.5%; p = 0.04), and rates of overall response (OR) in the groups were 37.1% vs. 19.4% (p = 0.11). No increase in toxicities was observed in the Ipi-RT group compare with ipilimumab alone. Prospective trials are needed to further clarify the role of radiotherapy with ipilimumab, but these encouraging preliminary observations suggest that this combination can induce more durable responses to immunotherapy.