ALBERT

Description: Second autologous stem cell transplant (ASCT) is a treatment option for multiple myeloma (MM) patients (pts) who have disease progression after first ASCT. About 20% of MM pts have evidence of renal dysfunction and many more develop it subsequently. Outcomes of second ASCT in pts with renal dysfunction have not been described. We identified 18 pts at our institution who underwent a second ASCT for relapsed MM and had evidence of renal dysfunction (creatinine clearance ≤ 60ml/min/1.73m2). Pts who underwent a planned tandem transplant were excluded from this analysis. Patient characteristics are shown in Table 1. The median age of pts was 61 years (range, 49-72). The median time between first and second ASCT was 49.8 months (range, 19.2-81.9). Ten pts received one chemotherapy regimen while nine pts received two or more chemotherapy regimens between first and second ASCT. The chemotherapy regimens used between first and second transplant included IMid based (n=6), proteosome inhibitor based (n=3) and combination of both (n=9). Approximately half of the pts had progressive disease at the time of second ASCT. Median creatinine clearance at the time of second ASCT was 43.5 ml/min//1.73m2. All pts received G-CSF 5µg/Kg from day + 6 till absolute neutrophil count was ≥1500/µL, norfloxacin, acyclovir and fluconazole were used for antimicrobial prophylaxis during the hospitalization. One pt was dialysis dependent. Patients received a median dose of melphalan of 140mg/m2 (range 100-200 mg/m2). Median follow up post second ASCT was 17.1 months (range, 2.4- 100). One pt died 74 days after the transplant due to multi- organ failure. Disease status at day 100 post ASCT is shown in Table 2. Thirteen of 17 pts had a partial response or better after second ASCT. Of 17 evaluable pts at day 100, twelve had an upgrade from the disease response category achieved with the last regimen used prior to second ASCT while five pts had stable disease response. Three pts received maintenance therapy after the second ASCT with bortezomib(n=2) and lenalidomide (n=1). Figures 1 and 2 show the overall survival (OS) and relapse free survival (RFS). Median RFS was 22.2 months and median OS was 27 months. The outcomes of patients with renal dysfunction who underwent ASCT in the era of novel agents at our institution are comparable to those reported for second ASCT. The transplant related mortality was not higher than expected and the median PFS of about 2 years makes the option of second ASCT in this group of patients a valuable treatment modality. The utility of maintenance therapy after the second ASCT is not established, but may have contributed to the durable responses seen in some pts assessed herein and deserves to be investigated further. Table 1: Pt Characteristics (N=18) Patient Characteristics N (%) Median Age (range) 61 years(49-72) Median Time from First ASCT (range) 49.8 months(19.2-81.9) Gender Male 9(50%) Females 9 (50%) Race Caucasians 13 (72%) Others 5 (28%) Disease status at time of ASCT PD 9 (50%) SD 5 (28%) PR 1 (5.5 %) VGPR 2 (11%) CR 1 (5.5%) Median creatinine clearance (range) 43.5 (5-59) Subtype IgG Kappa 10 (56%) IgG Lambda 6 (33%) Kappa Light Chain 2 (11%) Cytogenetic Risk Standard 10 (56%) High Risk 4(22%) Unknown 4 (22%) Melphalan Dose median mg/m2( range) 140 (100-200) {100(2pts), 140(10pts), 180(1pt), 200(4pts)} Median CD 34 Cell dose x106/kg (range) 4.66(2.6-27.5) Median Engraftment Day (range) WBC 11 (9-16) Platelets 21 (12-61) Median Days of Hospitalization (range) 19(11-74) PD: Progressive disease, SD: Stable disease; PR: Partial response; VGPR: Very good partial response; CR: complete response; WBC White blood cells Table 2 Disease status at Day 100 post ASCT Disease status at Day 100 post ASCT N(%) CR 4 (22%) VGPR 4 (22%) PR 5 (28%) SD 3 (17%) PD 1 (5.5%) NOT AVAILABLE * 1 (5.5%) PD: Progressive disease, SD: Stable disease; PR: Partial response; VGPR: Very good partial response; CR: complete response; *Pt died at day 74 post second ASCT PD: Progressive disease, SD: Stable disease; PR: Partial response; VGPR: Very good partial response; CR: complete response; * Pt died at day 74 post second ASCT Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Description: Introduction Prophylactic platelet transfusions are often performed prior to bronchoscopy or broncho-alveolar lavage (BAL) to prevent bleeding in thrombocytopenic patients. There is a paucity of data to validate this approach, with a platelet transfusion threshold of 2.0) and coagulation studies (PT, PTT, INR) were identified. The British Thoracic Society guidelines1 were used to categorize bleeding as a result of bronchoscopy. Data were analyzed using descriptive statistics. Results The median age was 59 years (range 27-90), with two-thirds of patients (63%) being male. One hundred and seventeen (78%) patients had underlying malignancy and 55 (37%) had thrombocytopenia related to malignancy. Fellows and residents under the supervision of a bronchoscopy certified attending performed all but 4 of the bronchoscopies. Infection (40%) was the primary indication for bronchoscopy with BAL performed in 127 (85%) patients. Fifty-eight of 89 (65%) patients with baseline platelet counts 50,000/mm3. The platelet count did not rise to 〉50,000//mm3 in many transfused patients. Seventy patients (47%) had counts 50,000/mm3 at the time of bronchoscopy. 49% were receiving immunosuppressive medications, 45% had renal dysfunction and 8% had INR 〉1.5. Bloody lavage that resolved spontaneously without continuous suctioning (Grade 0) was observed in 9 (6%) patients. Bleeding that required continuous suctioning but then resolved spontaneously (Grade 1) was noted in 1 patient with a platelet count of 61,000/mm3. Of 10 total bleeding events, 7 occurred in patients who were intubated. Two additional patients with platelet counts of 30,000/mm3 and 53,000/mm3 had diffuse alveolar hemorrhage, which was present before bronchoscopy. “Old” blood and blood clots were observed in 6 patients. Discussion The low incidence of bleeding complications from bronchoscopy +/- BAL even in patients with platelet counts

Description: Approximately 20% of Multiple Myeloma (MM) patients (pts) have renal dysfunction(RD) at the time of diagnosis and some more may develop it during the course of their disease. Autologous stem cell transplant (ASCT) is a treatment modality for this incurable malignancy and there are ongoing studies to determine the optimal timing of ASCT in this disease. There are conflicting data regarding the outcomes among different racial groups with regards to ASCT in MM. In this restrospective review we studied outcomes in pts of different races with RD undergoing ASCT for MM. Between June 2005 and December 2013, we identified 107 pts with MM with RD (creatinine clearance 〈 60 ml/min/1.73 m2) who were not on hemodialysis and underwent ASCT at our institution. Of the 107 pts, 76 were caucasian(C) pts and 31 were identified as other (O) races (25 African American, one Hispanic, two Middle-eastern, three Asian). The patient characteristics of both groups are shown in Table 1. There were no statistically significant differences in the characteristics between the 2 groups. Approximately a quarter of the pts received their melphalan dose on the inpatient unit in both groups. During the hospitalization all pts received G-CSF from Day +6 till absolute neutrophil count ≥ 1500/µl and antimicrobial prophylaxis with norfloxacin, acyclovir and fluconazole. The median follow up was 35.9 months (range, 5.1-106.3). One patient in the C group died 98 days after ASCT and had evidence of disease progression. There were no deaths in the O group during the 100 days after ASCT. Table 2 shows post ASCT disease status and details about post ASCT maintenance therapy. There were no statistically significant differences between the groups in disease status or change in disease status at day 100 post ASCT. Although more patients in the C group received maintenance therapy post ASCT, this difference was not statistically significant. Figures 1 and 2 show the relapse free survival (RFS)and overall survival (OS) of both groups. The median RFS for C and O groups were 32.3 and 20.9 months (p =0.63, log rank), respectively. The median OS of the C and O groups were 73.1 and 47.8 month (p=0.31, log rank), respectively. Our limited experience suggests that there was no effect of race in the post ASCT outcomes for MM pts with RD. ASCT was safe with acceptable transplant related mortality and good long -term outcomes for MM pts with renal dysfunction. Table 1: Patient Characteristics (N=107) Patient Characteristics Caucasians (n=76) Others (n=31) Median Age (range) 63 (36-73) 64(28-73) 0.58 Gender Male 42 (55%) 17 (55%) 0.9 Females 35 (45%) 14 (45%) Chemo regimens prior to ASCT 1 51 (67%) 21 (68%) 0.95 ≥ 2 25 (33%) 10 (32%) Agents used prior to ASCT IMid 12 (16%) 4 (13%) 0.85 PI 18 (24%) 9 (29%) Both 46 (60%) 18 (58%) Disease status at time of ASCT PD 7 (10%) 5 (16%) 0.35 SD 9 (12%) 4 (13%) PR 20 (26%) 11 (35%) VGPR 20 (26%) 8 (26%) CR 20 (26%) 3 (10%) Median creatinine clearance (range) 45.5 (15-60) 43 (21-60) 0.35 Subtype* IgG Kappa 29 (34%) 18 (58%) 0.25 IgG Lambda 18 (24%) 6 (19%) Ig A Kappa 9 (12%) 2 (6%) Ig A Lambda 5 (7%) 3 (10%) K Light Chain 6 (8%) 0 L Light Chain 5 (7%) 0 Non- Secretory 3 (4%) 2 (6%) Cytogenetic Risk Standard 65 (85%) 18 (58%) 0.67 High Risk 5 (7%) 2 (6%) Median Melphalan Dose mg/m2 (range) 140 (140-200) {140(58),160(5), 180(4),200(9)}® 140 (100-200) {100(2),140(25), 200(9)} 0.89 Administration of Melphalan Inpatient 18 (24%) 9 (29%) 0.56 Outpatient 58 (76%) 22 (71%) Median CD 34 Cell dose x106/kg (range) 3.3 (2 -10.1) 3.9 (2.3-9.5) 0.34 Median Engraftment Day (range) Neutrophil 12 (11-20) 12(10-27) 0.86 Platelets 18(11-88) 17 (11-42) 0.10 Median Days of Hospitalization (range) 15 (9-65) 16 (12-55) 0.96 * 1 pt each in the caucasian group had IgD Lambda and IgM Kappa paraprotein ® Pts received 160 and 180 mg doses as part of a study PI: proteosome inhibitors, PD: progressive disease, SD: stable disease, PR: partial response, VGPR: very good partial response, CR: Complete response Table 2: Disease status at Day 100 post ASCT Caucasian (N=76) Other (N=31) P Value Disease Status CR 26 (34%) 6 (19%) 0.5 VGPR 20 (26%) 12 (38%) PR 17 (22%) 6 (19%) SD 7 (9%) 4 (13%) PD 2 (3%) 2 (7%) Not available 4 (6%) 1 (3%) Change in Disease Status Improved 23 (30%) 13 (42%) 0.66 Unchanged 45 (59%) 15 (48%) Worsened 4 (6%) 2 (7%) Not available 4 (6%) 1 (3%) Maintenance Therapy IMid 40 (53%) 9 (29%) 0.15 PI 2 (3%) 1 (3%) None 29 (38%) 19 (61%) Not Known 5 (7%) 2 (7%) Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Description: About 5% of patients with Multiple Myeloma (MM) have evidence of severe renal dysfunction requiring hemodialysis (HD) at the time of diagnosis. Often, patients on HD are not referred for autologous stem cell transplant (ASCT) due to the concern of higher treatment-related mortality. There is a dearth of data regarding outcomes in patients on HD who undergo ASCT in the era of novel agents. We conducted a retrospective chart review of fifteen patients on HD who underwent their first ASCT at our institution from June 2005 to December 2013. The patient characteristics are shown in Table 1. All patients had novel drugs for induction therapy prior to ASCT; thirteen patients had received 3 drug regimens and 2 patients had received 2 drug regimens. Eight patients received regimens containing both Lenalidomide and Bortezomib, five received Bortezomib-based regimens and one received Lenalidomide-based regimens. Three patients received more than one regimen. The median time from diagnosis to ASCT was 9.9 months (range, 4.7-33.1). Median patient follow-up was 18 months (range, 0.2-82 months). One patient died 7 days after transplant due to sepsis resulting in multi-organ failure. All patients received Melphalan in the inpatient unit. All patients received G-CSF 5µg/Kg from day + 6 till ANC 1500/ µL. Norfloxacin, acyclovir and fluconazole were used for antimicrobial prophylaxis during hospitalization. Two patients (13%) were able to stop dialysis after ASCT. The disease status of all patients at day 100 is shown in Table 2. At the day 100 assessment of 14 evaluable patients, five had an upgrade in the disease response and nine had no change. Seven patients received maintenance therapy after ASCT with Lenalidomide (6) and Bortezomib (1). Figures 1 and 2 display the Kaplan-Meier curves for overall survival (OS) and relapse free survival (RFS). The median OS of these patients at 5 years was 59% and RFS was 37 months. Our experience in HD patients who underwent ASCT for MM with the use of novel agents during induction suggests that ASCT is safe with acceptable toxicity and a median RFS is about 3 years. The relapse-free survival could be improved with the use of novel agents for maintenance therapy in more patients. The application of novel agents during induction and maintenance therapies may be responsible for improving outcomes in these patients. Table 1: Patient Characteristics Patient Characteristics N (%) Median Age (range) 51 (31-67) Gender Male 11 (73%) Females 4 (27%) Race Caucasians 8 (53%) Others 7 (47%) Disease status at time of ASCT SD 1 (7%) PR 7 (47%) VGPR 4 (27%) CR 3 (19%) Median creatinine clearance (range) 9 (3-43) Subtype IgG Kappa 7 (47%) IgG Lambda 3 (19%) Kappa Light Chain 2 (13.5%) Lambda Light Chain 2 (13.5%) Non- Secretory 1 (7%) Cytogenetic Risk Standard 11 (73%) High Risk 2 (13.5%) Unknown 2 (13.5%) Median Melphalan Dose mg/m2 (range) 140 (100-140) (One patient received 100 mg/m2) Median CD 34 Cell dose x106/kg (range) 3.34 (2.31-4.96) Median Engraftment Day (range) WBC 13 (11-14) Platelets 24 (17-89) Median Days of Hospitalization (range) 20 (9-34) SD: stable disease; PR: partial response; VGPR: very good partial response; CR: complete response Table 2: Disease status at Day 100 post ASCT Disease Status PR 3 (19%) VGPR 10 (67%) CR 1 (7%) Not available 1 (7%) Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.