Influence of Race on Outcomes in Multiple Myeloma Patients with Renal Dysfunction Undergoing High Dose Therapy Followed By Autologous Stem Cell Transplant

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5904-5904
Author(s):  
Lakshminarayanan Nandagopal ◽  
J. Christine Ye ◽  
Marie Ventimiglia ◽  
Muneer H. Abidi ◽  
Lois Ayash ◽  
...  

Abstract 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.

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8596-8596
Author(s):  
N. Shah ◽  
D. Weber ◽  
R. Orlowski ◽  
M. Wang ◽  
S. K. Thomas ◽  
...  

8596 Background: The introduction of novel therapeutic options with bortezomib and immunomodulatory agents in the up-front management of multiple myeloma (MM) has significantly improved induction response rates. However, the role of high dose chemotherapy and autologous stem cell transplant (ASCT) after induction with these highly active agents is not known, especially in patients with only a partial response to induction therapy. Methods: We conducted a retrospective review of 95 newly diagnosed MM patients treated with induction bortezomib-lenolidomide-dexamethasone (BLD) or bortezomib-thalidomide-dexamethasone (BTD) prior to ASCT. Responses were graded according to IMWG criteria. Results: 19 patients received BLD and 76 patients received BTD. All patients were conditioned with a melphalan-based regimen. Of the 19 patients who underwent induction with BLD, complete response (CR), very good partial response (VGPR) and partial response (PR) were achieved in 2 (11%), 8 (42%) and 9 (47%) respectively for an overall response rate (ORR) of 19/19 (100%). After ASCT, CR, VGPR and PR were achieved in 9 (47%), 5 (26%) and 5 (26%) respectively for a continued ORR of 21/21 (100%). Notably, 4/8 (50%) of patients with a VGPR after induction therapy with BLD improved to a CR after ASCT. 3/9 (33%) of patients with an initial PR to BLD improved to a CR and 1/9 (11%) with a PR improved to VGPR after ASCT. Of the 76 patients who underwent induction with BTD, CR, VGPR and PR were achieved in 6 (8%), 37 (49%) and 31(41%) respectively for an ORR of 74/76 (97%). 1 patient had stable disease and 1 patient had progressive disease. After ASCT, 27/76 (36%) achieved a CR, 30/76 (39%) a VGPR and 18/76 (24%) a PR for an ORR of 75/76 (99%). Of the patients who initially had a VGPR to BTD 16/37 (43%) improved to a CR while 5/32(16%)of PR patients improved to a CR and 9/32 (28%) of PR patients improved to a VGPR. Conclusions: Of the 40 patients who only achieved a PR after induction therapy with BLD or BTD, 16 (40%) had further improvement to a CR or VGPR after ASCT. Thus there is a significant benefit of ASCT in these patients who initially demonstrate relative resistance to induction therapy with highly active regimens. [Table: see text]


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2399-2399 ◽  
Author(s):  
Firoozeh Sahebi ◽  
Amrita Krishnan ◽  
Leonardo Farol ◽  
Ji-Lian Cai ◽  
George Somlo ◽  
...  

Abstract Abstract 2399 The quality and depth of response particularly achievement of complete remission (CR) have been associated with significant improvement in progression free survival (PFS) and overall survival in multiple myeloma patients undergoing autologous stem cell transplant. Achievement of CR is considered a valid surrogate endpoint for survival in clinical trials for patients with multiple myeloma. We performed a phase II study investigating the role of sequential bortezomib/dexamethasone followed by thalidomide/dexamethasone as maintenance therapy post single autologous PSCT. The objectives were to examine the feasibility, toxicities, CR, PFS and overall survival rates. Within 4–8 weeks of autologous PSCT using melphalan 200mg/m2, pts received weekly bortezomib (bor) at 1.3mg/m2 /wk × 3 weeks with 1 week rest and dexamethasone (dex) at 40mg/d × 4 d for 6 months, followed by thalidomide (thal) at 50 –200mg/d and dexamethasone (dex) at 40mg/dx4 d for 6 more months. Single agent thalidomide was then continued until disease progression. Between March 2008 and June 2010, forty-five pts were enrolled. Median age was 54 years (29-71). Median time from diagnosis was 6.1 mo. (3.5 – 145.9). Disease stage at diagnosis; by Salmon-Durie (I/II/III 2/8/34/1 not available) and by ISS (I/II/III 18/14/8/ 5 not available). Pts received prior induction treatment with thal/dex (15), bortezomib based (27) and lenalidomide based regimens (10). Median B2M at enrollment was 1.8 mg/L (1.05 -5.3). Disease status at enrollment included complete remission (CR) (11), very good partial response (VGPR) (11), partial response (PR) (23). Six pts had chromosome 13 abnormalities (1 pt by karyotype and 5 pts by FISH), 2 pts had t 4;14 (one with concurrent ch 17 p del) and 3 pts had complex cytogenetic abnormalities. Results: Forty-five pts have been enrolled and undergone transplant. Five pts were unable to start planned maintenance therapy due to development of grade II or more neuro toxicities (4), and persistent thrombocytopenia (1) after PSCT. Thirty nine pts started maintenance bor/dex within 4–8 weeks of PSCT. One pt is too early for maintenance therapy. Twenty-five pts have completed the planned 6 months of bor/dex. Ten pts stopped bor/dex because of low WBC (2), PN (4), diagnosis of adrenal cancer (1), myocardial infarction (MI) (1), and relapse (2). Six pts are still receiving maintenance bortezomib. With a median F/U of 8.5 mo. (0.2 -24.0) twelve of 44 evaluable pts (27%) have achieved CR post PSCT and 17 of 33 evaluable pts (51%) have achieved CR after bor/dex on an intention to treat (ITT) analysis. Fifteen of 25 pts (60%) who have completed 6 months of bor/dex have achieved CR. Nine of 25 pts (36%) have upgraded their response with bor/dex. Eight pts (24%) could not complete bortezomib due to toxicities. At one year post PSCT fourteen of 28 evaluable pts (50%) remain in CR. Six pts have relapsed of whom 2 died of relapsed myeloma (leptomeningeal disease 1 pt). One pt experienced MI while receiving bortezomib (grade IV). Grade III toxicities have occurred in 17 pts; low platelet (1), asthenia (2), mood alteration (1), GI (severe constipation due to partial bowel obstruction on thalidomide) (1), skin rash (1), hyperglycemia (1), lymphopenia (10), sinus bradycardia (1), elevated triglyceride (1), DVT (1), low phosphate (3), leukopenia (1), edema (1). Sixteen pts had peripheral neuropathy (PN) grade I prior to start of bortezomib. Only 8 pts have developed new PN on the study and all are grade I-II. No patient has experienced grade III-IV PN. Median bortezomib dose is 1.3 mg /m2 per week. Conclusion: Prolonged weekly bortezomib maintenance therapy is well tolerated and can upgrade response post single autologous PSCT with no severe peripheral neuropathy. Fifty one percent of pts have achieved CR and 36% have upgraded their response after six months of bortezomib/dexamethasone therapy suggesting this is an active maintenance strategy post PSCT. Disclosures: No relevant conflicts of interest to declare.


2018 ◽  
Vol 23 (6) ◽  
pp. 734-739 ◽  
Author(s):  
Elizabeth Dianne Pulte ◽  
Andrew Dmytrijuk ◽  
Lei Nie ◽  
Kirsten B. Goldberg ◽  
Amy E. McKee ◽  
...  

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2518-2518
Author(s):  
J. Christine Ye ◽  
Lakshminarayanan Nandagopal ◽  
Marie Ventimiglia ◽  
Muneer H. Abidi ◽  
Lois Ayash ◽  
...  

Abstract 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.


2019 ◽  
Vol 55 (6) ◽  
pp. 1188-1190
Author(s):  
Mark A. Fiala ◽  
Venkata Vosuri ◽  
Scott Goldsmith ◽  
Mark A. Schroeder ◽  
Armin Ghobadi ◽  
...  

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