Chaudhry, Hafsa

Abstract Aims: Autologous stem cell transplantation (ASCT) is an important component in the treatment of newly diagnosed multiple myeloma (MM). However, relapse following ASCT is considered almost inevitable, with a median time to progression (TTP) of approximately 23-26 months (without maintenance) and 40-46 months (with maintenance)(Attal MA et al. N Engl J Med 2012; 366:1782-1791; McCarthy PM et al. N Engl J Med 2012; 366:1770-1781). However, some patients can experience a prolonged period of remission with ASCT. The purpose of this study was to identify and characterize patients who have an exceptional response to upfront ASCT without maintenance therapy, and to determine the frequency of relapse in such patients. Methods: We searched the Mayo Clinic Multiple Myeloma bone marrow transplant database for patients who were diagnosed with MM between Aug 1, 1988 to Jan 3, 2006, and underwent ASCT within 12 months of initial diagnosis. For the purposes of this study, we defined exceptional responders as patients who were free of progression for 96 months or more, which is 2-3 fold more than the median TTP expected in this population. Since maintenance therapy was not standard of care at the time, only a small minority (6) of patients with prolonged TTP had received maintenance therapy; these patients were excluded since the study was focused on exceptional response with ASCT alone. One patient who had a tandem autologous transplant was excluded. Results: 509 patients underwent transplant during the study period. Of those, 46 (9%) met criteria for exceptional response. Twenty seven (59%) were female, 19 (41%) were male. Median age was 57.28 years, range, 31.9-73.0. Of 45 patients with response data available, the best response status was complete response or better in 32 patients (73.3%), VGPR in 4 patients (8.9%), and PR in 8 patients (17.7%). FISH data were available during the disease course for 41 patients. Of these, the majority, 28 patients (68.3%), had no abnormalities detected by the probes used; 3 patients (7.3%) had high risk cytogenetics (t(4;14) in 2 patients and t(14;16) in one patient) , 4 (9.8%) had trisomies; 6 patients had other isolated abnormalities. At last follow up, 23 patients have progressed (50%); 14 (30.4%) have died, including one who died without progression to MM. The median overall survival from time of diagnosis of the exceptional responders was 18.5 years, range 9.2-22 years. From the landmark time of 96 months, the median TTP was 6.2 years, range, 0.4-10.6 years (Figure 1); No plateau was seen in the TTP curve. From the landmark time of 96 months, the median OS was 10.5 years, range, 0.4-14 years. Conclusions: We conclude that approximately 10% of patients with newly diagnosed myeloma have an exceptional response to a single ASCT without maintenance therapy. These patients have a remarkable overall survival, both from diagnosis and from the landmark time point where they are classified as having achieved an exceptional response. Although TTP from the landmark time point is excellent, with median TTP of 6.2 years, there appears to be no plateau in the curve indicating ongoing risk of relapse despite a prolonged period of disease stability. Exceptional responders tended to have normal FISH studies (likely an indicator of responsive, low-tumor burden disease), and nearly 20% achieved this state despite not attaining a complete response. Figure. Figure. Disclosures Gertz: Research to Practice: Consultancy; Apellis: Consultancy; spectrum: Consultancy, Honoraria; Medscape: Consultancy; celgene: Consultancy; janssen: Consultancy; Teva: Consultancy; Abbvie: Consultancy; annexon: Consultancy; Ionis: Honoraria; Alnylam: Honoraria; Prothena: Honoraria; Amgen: Consultancy; Physicians Education Resource: Consultancy. Kumar:KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Dispenzieri:Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSK: Research Funding. Dingli:Millennium Takeda: Research Funding; Millennium Takeda: Research Funding; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.. Russell:Vyriad: Equity Ownership. Kapoor:Takeda: Research Funding; Celgene: Research Funding.

Abstract Introduction Polycythemia vera (PV) and Essential thrombocytosis (ET) progress to myelofibrosis (MF). Extramedullary hematopoeisis (EMH) is common in patients with primary or secondary MF, and can occur in the lungs. Pulmonary EMH can cause recurrent pleural effusions, pulmonary hypertension, and right heart failure with symptoms of dyspnea, cough, and fatigue. Low dose single fraction whole lung irradiation (WLI) has been utilized at our institution, and our preliminary report of 4 patients noted symptomatic improvement with no reported acute side effects. Here we report on a larger cohort of 57 patients as well as long term outcomes for 20 of those patients, including the original 4 patients. Methods We performed a retrospective review of 57 patients with myelofibrosis and pulmonary EMH who received single fraction WLI to a dose of 100 cGy at the Mayo Clinic from March 2001 to March 2014. Data related to the following parameters was collected: initial diagnosis, age at initial diagnosis, date of progression to myelofibrosis, initial treatment prior to radiation therapy, whole body bone marrow scan findings if available, and response to WLI. Overall survival was measured using the Kaplan Meier method. Chi-square analysis was used to evaluate predictors of response to WLI. Results The median age at first WLI was 67 years (45-84 years), and 33 patients (58%) were male. Twenty-two patients (39%) had a diagnosis of primary MF, 27 patients (47%) had PV or ET, and 8 patients (14%) had another cause of secondary MF. At the time of WLI, 27 patients (47%) were on supplemental oxygen, and 3 patients (5%) were in the intensive care unit. Hydroxyurea (n=14, 25%), JAK2 inhibitors (n=9, 16%), Anagrelide (n=3, 5%), and Thalidomide and Prednisone (n=3, 5 %) were the most frequent treatments prior to WLI. EMH was confirmed on bone scan in 38 patients (67%). In the remaining 19 patients, a diagnosis of EMH was made based on clinical impression. This included symptoms of dyspnea, cough, and fatigue, echocardiographic findings of pulmonary hypertension, and in some patients recurrent pleural effusions (n=13), positive lymph node biopsy (n=2), or thoracentesis (n=1). Twenty-eight (49%) patients had other active cardiac or pulmonary conditions that likely contributed to their clinical symptoms. These patients were receiving concurrent treatment for their other conditions. In some patients there were multiple coexisting conditions. Clinical improvement occurred in 30 patients (53%). The median time from WLI to symptomatic improvement was 10 days (1-174 days). Twenty-four patients (42%) did not have clinical improvement. Nine patients (16%) had stable symptoms, 15 patients (26%) had progressive symptoms, and 3 patients (5%) had insufficient follow up. In the group of patients with concurrent active cardiac or pulmonary conditions, 15 patients (54%) had clinical improvement following WLI. In the 29 patients who had solitary EMH, 15 (52%) patients had clinical improvement. There was no difference in response rates related to oxygen use at the time of WLI. Six patients (11%) received WLI on multiple occasions. There was no difference in the percentage of patients with positive bone marrow scans (67%) in the 2 groups. The median overall survival was 259 days for all patients. Patients who improved after WLI had a median survival of 325.5 days compared to 122.5 days for patients who did not improve. No new hematologic abnormalities temporally related to WLI were reported. Long term follow up beyond 1 year was available for 20 patients (35%). No patients developed pneumonitis or pulmonary fibrosis that was considered related to WLI. One patient received a diagnosis of an upper esophageal squamous cell carcinoma 6 years after WLI and allogeneic stem cell transplant. Conclusion Our prior study showed WLI is safe and effective in a small number of patients with isolated pulmonary EMH from MF. The current study confirms the long term safety of this approach. Our results suggest WLI may contribute to symptomatic improvement in 1/2 of patients, even in the common clinical situation of multiple coexisting cardiac and pulmonary conditions. Repeat WLI is also well tolerated and can result in symptomatic improvement. We did not find any factors that predicted response to WLI. WLI should be considered in patients who have clinically proven pulmonary EMH and associated symptoms, even in the presence of other conditions, and can be repeated safely. Disclosures No relevant conflicts of interest to declare.

Background Patch-test readings after day 5 have previously been used to identify delayed reactions to metals and topical antibiotics. Objective The aims of this study were to identify allergens for which late readings (beyond day 5) would be most valuable and to compare our results with our previous study on delayed patch-test readings. Methods This was a retrospective study of 298 patients who underwent metal and corticosteroid series patch testing from January 1, 2007, through December 31, 2013. Patch-test readings were conducted on days 3 and 5 and at least once sometime between days 7 and 14. All reactions were examined at each reading. Conclusions These results were concordant with our previous findings that additional readings after day 7 are particularly useful for identifying reactions to metals (gold, cobalt, beryllium, palladium), specific preservatives (dodecyl gallate, propolis), and the topical antibiotic neomycin. New delayed reactions to bacitracin, p -phenylenediamine, and topical corticosteroids were not seen in this cohort.