Sposto, Richard

Abstract Abstract 601 Background: Despite therapeutic advances and availability of novel agents, multiple myeloma (MM) remains an incurable malignant disorder and strategies to improve survival are being actively sought. One such approach is the use of maintenance therapy with lenalidomide (Revlimid®; R), which has shown PFS benefit, without conclusive evidence of OS benefit except in a selected population (CALGB100104). Shrinking resources with rising healthcare costs warrant careful assessment of the financial impact of expensive anticancer therapeutics in context with the true benefit to patients. Methods: This analysis was not supported or solicited by any pharmaceutical industry. For our pharmacoeconomic study we selected the MM-015 trial; a large (n=459) double-blind, randomized, placebo-controlled phase III study that investigated the efficacy of continuous R maintenance after initial therapy with melphalan/prednisone/lenalidomide (MPR) in a uniform cohort of patients (≥65 years, newly diagnosed MM, transplant ineligible). The three study arms were MP, MPR and MPR followed by R maintenance (MPR-R). The cost-effectiveness model included medical costs (drugs, office visits, laboratory tests) and costs of treatment-related adverse events (AEs) for an individual patient. Drug costs were calculated from the average wholesale price, using average US adult weight of 80kg. Office visit and laboratory test costs were obtained using Medicare reimbursement fees. Costs of AEs were obtained from peer-reviewed publications. Incidence of AEs was obtained from the published MM-015 trial. Costs were valued in 2011 US dollars. Cost calculations included: (1) computing distribution of the numbers of induction and maintenance courses completed by patients treated with each of these regimens; (2) computing the per-course probabilities of the occurrence of individual AEs during induction and maintenance for each of these toxicities; (3) combining these data with the treatment costs and costs of individual AEs to compute cumulative cost of treatment through 40 maintenance cycles and cumulative cost of treatment per progression-free survivor. Summary measures computed for each treatment: (1) average cumulative cost per patient (ACCP) treated; (2) average cumulative cost per progression free survivor (ACCPFS), representing the average cumulated cost/patient who is progression free at that time. The distribution of courses received was obtained from the MM-015 publication. Data on subsequent therapy at the time of disease progression was not available. Results: Median follow up reported in the published study was 30 months. Median PFS was 13 months (MP), 14 months (MPR) and 31 months (MPR-R) in the three arms. Table 1 summarizes the calculated ACCP and the ACCPFS of each regimen for induction and maintenance treatment. MPR-R was the most expensive of the three arms in terms of total cumulative costs, with an ACCP of $231,314, compared to $166,211 for MPR and $17,972 for MP. However, taking the efficacy of each regimen into account (ACCPFS), MPR greatly exceeds both MPR-R and MP ($1,540,139 vs. $516,322 vs. $309,346), while the difference between MPR-R and MP was less distinct. Figure 1 illustrates the exponential increase in ACCPFS of MPR, compared to MPR-R and MP. Conclusions: From a cost-effectiveness perspective, if MPR is used as the induction regimen, maintenance with R should be strongly considered, as MPR without maintenance does not confer any significant benefit over MP, while incurring a much higher cost. However, the overall cost of MPR-R is substantial with no reported OS benefit at present. In the absence of clear survival benefit the financial burden of prolonged treatment becomes an important factor to consider prior to adopting this therapeutic strategy in MM. As part of a global strategy for addressing healthcare costs, it is important to consider this in appropriate medical decision making for patients, and to include cost-effectiveness analyses as a part of large prospective clinical trial efforts. Disclosures: No relevant conflicts of interest to declare.

10512 Background: Inotuzumab ozogamicin (InO), a CD22-targeting antibody linked to calicheamicin demonstrated exceptional activity in R/R ALL in adults. InO has been available to pediatric patients with R/R ALL via a compassionate access program. Methods: Participating international pediatric oncology centers received IRB approval to submit retrospective demographic, outcome and toxicity data on pediatric patients who received at least one dose of InO. Results: Thirty-four patients, age 2.3-21.4 yrs (median 11.7) received 1-4 cycles (3 weekly doses) of InO. Patients were heavily pretreated in 1st-5threlapse; 28 were refractory to their preceding regimen. Thirteen patients had prior hematopoietic stem cell transplant (HSCT), 27 received prior CD19 and 8 prior CD22-directed therapy. Pre-InO disease was M3 ( > 25% blasts) in 26 patients, M2 (5-25%) in 3, and MRD only in 5 (1 with extramedullary disease). Of 29 patients with M2/M3 disease at baseline, 18 (62%) achieved a complete remission (CR), 13 of whom were MRD negative. Post-InO, 15 patients proceeded to HSCT and 5 to CAR T-cell therapy. Alterations in CD22 expression at subsequent relapse were noted in two patients with available blasts samples. No deaths were attributed to InO during therapy. The incidence of grade 3/4 infections was 38% and were of the expected types. Grade 1-4 hepatic toxicity was noted in 11/34 (32%) patients, primarily asymptomatic elevations in transaminases/bilirubin. There was no sinusoidal obstruction syndrome (SOS) during InO therapy but 8/15 patients who received HSCT post-InO developed SOS. One patient died from SOS, but the others recovered. The incidence of SOS was higher in patients who had undergone prior HSCT (6/8) versus no prior HSCT (2/7). SIRS (1), neurotoxicity (2) and hemorrhage (3) were infrequent. Three patients had musculoskeletal pain associated with edema. Conclusions: Single agent InO had a CR rate of 62% in heavily pretreated pediatric patients. Toxicities were similar to adults with hepatic and infectious toxicity being the most common. Overall InO was well tolerated, but the incidence of SOS was high in patients who underwent HSCT post-InO, particularly in those who had undergone a prior HSCT.

PURPOSE: To determine the toxicity and response rate in children treated with dexamethasone, etoposide, cisplatin, high-dose cytarabine, and l-asparaginase (DECAL) for recurrent non-Hodgkin’s lymphoma (NHL) and Hodgkin’s disease (HD). PATIENTS AND METHODS: Ninety-seven children with recurrent NHL (n = 68) or HD (n = 29) were enrolled. Treatment consisted of two cycles of DECAL, then bone marrow transplantation or up to four cycles of ifosfamide, mesna, and etoposide alternating with DECAL maintenance therapy. RESULTS: After two cycles of DECAL induction therapy, complete response (CR) or partial response (PR) was reported in 19 (65.5%; 10 CRs and nine PRs) of 29 patients with HD and 29 (41.6%; 23 CRs and six PRs) of 68 patients with NHL. When only 24 patients with HD and 58 patients with NHL who were assessable for response were considered, the response rates were 79.2% (19 of 24 patients) and 50.0% (29 of 58 patients), respectively. Five-year event-free survival was 26% ± 9% and 23% ± 5% in patients with HD and NHL, respectively. Five-year survival was 31% ± 14% and 30% ± 6%, respectively. Although median time to treatment failure was significantly longer in patients with HD (EFS, P = .002; survival, P = .011), this difference did not translate into a higher long-term survival. Grade 3 or 4 toxic effects were observed during induction in 70 (72%) of 97 patients and during maintenance in 45 (70%) of 64 courses of DECAL therapy. Pancytopenia and systemic infections in particular were frequently observed. Other toxic effects were uncommon. Although not a formal part of the therapy or the study design, 42 patients who responded to therapy who underwent bone marrow transplant did not show any benefit from this approach. CONCLUSION: DECAL is an effective and tolerable salvage regimen for treating patients with recurrent NHL and HD.

Purpose In 1995, the Children's Cancer Group (CCG) opened a trial for patients with Hodgkin's lymphoma evaluating whether low-dose involved-field radiation therapy (IFRT) improved event-free survival (EFS) for patients achieving a complete response after chemotherapy. We present the long-term study outcome using final data through March 2007. Patients and Methods Between January 1995 and December 1998, 826 eligible patients were enrolled onto CCG 5942. Four hundred ninety-eight patients achieving an initial complete response to chemotherapy were randomly assigned to receive IFRT or no further therapy. EFS and overall survival (OS) were assessed from the date of study entry or random assignment, as appropriate. Results Ten-year EFS and OS rates for the entire cohort were 83.5% and 92.5%, respectively. In an as-treated analysis for randomly assigned patients, the 10-year EFS and OS rates were 91.2% and 97.1%, respectively, for IFRT and 82.9% and 95.9%, respectively, for no further therapy. For EFS and OS comparisons, P = .004 and P = .50, respectively. Bulk disease, “B” symptoms, and nodular sclerosis histology were risk factors for inferior EFS. Conclusion With a median follow-up of 7.7 years, IFRT produced a statistically significant improvement in EFS but no improvement in OS. For individual patients, the relative risks of relapse versus late effects of IFRT must be considered. Patient and disease characteristics and early response assessment will aid in deciding which patients are most likely to benefit from IFRT.

PURPOSE: Current standard therapy for children and adolescents with Hodgkin’s disease includes combination chemotherapy and low-dose involved-field radiation (LD-IFRT). Because radiation may be associated with adverse late effects, the Children’s Cancer Group (CCG) investigated whether radiation could be omitted in patients achieving a complete response to initial chemotherapy without jeopardizing the excellent outcome obtained with combined-modality therapy. PATIENTS AND METHODS: Between January 1995 and December 1998, 829 eligible patients were enrolled onto CCG 5942. A total of 501 patients who achieved an initial complete response after risk-adapted combination chemotherapy were randomized to receive LD-IFRT or no further treatment. Event-free survival (EFS) and overall survival were assessed from the date of study entry or the date of randomization, as appropriate. RESULTS: The projected 3-year EFS from study entry for the entire cohort was 87% ± 1.2%. Among patients who achieved a complete response to initial chemotherapy, 92% ± 1.9% of those randomized to receive LD-IFRT were alive and disease free 3 years after randomization, versus 87% ± 2.2% for patients randomized to receive no further therapy (stratified log-rank test; P = .057). With an “as-treated” analysis, 3-year EFS after randomization for the radiation cohort was 93% ± 1.7% versus 85% ± 2.3% for patients receiving no further therapy (stratified log-rank test; P = .0024). Three-year survival estimates for patients treated with and without LD-IFRT were 98% ± 1.1% for patients who received radiation and 99% ± 0.5% for patients who did not receive radiation. CONCLUSION: LD-IFRT after an initial complete response to risk-adapted chemotherapy improved EFS. At this time, there is no survival advantage for LD-IFRT, but follow-up remains short.