Zoledronic Acid Plus Thalidomide Is Safe and Well Tolerated When Used as Post-Autologous Stem Cell Transplant Maintenance Therapy in Patients with Nonprogressive Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2551-2551
Author(s):  
Andrew Spencer ◽  
A. Roberts ◽  
T. Neeman ◽  
S. Cremers ◽  
H. Schran ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Zoledronic Acid ◽  
Serum Creatinine ◽  
Potential Effect ◽  
Phase Iii ◽  
Cell Transplant ◽  
Serum Samples ◽  
To Receive ◽  
Over Time

Abstract Background: Thalidomide (THAL), an immunomodulatory agent with antiangiogenic properties, has become standard of care for patients with refractory or relapsed multiple myeloma (MM). Zoledronic acid (ZOL) is effective in preventing skeletal complications from MM, has cytotoxic effects, and enhances dexamethasone and THAL cytotoxicity in vitro (Ural A, et al. Int J Hematol.2003;78:443–449). However, reports have suggested that combining ZOL with THAL increases the risk of renal adverse events in MM patients. In the present study, the potential effect of this combination on renal function was investigated as part of a multicenter, randomized, phase III trial. The study design also allowed the investigation of a potential effect of THAL on serum PK of ZOL in a subgroup of patients. Methods: Patients with nonprogressive MM who had previously undergone autologous stem cell transplantation were randomized to receive either THAL 200 mg od or no THAL. All patients received ZOL 4 mg via 15-minute infusion every 28 days and prednisolone 50 mg every other day. Total treatment and observation period was 12 months. Creatinine was determined in all pre-infusion serum samples. PK (Cmax and AUC) was determined from serum samples collected over 48 hours after the first 2 infusions of ZOL. The potential effect of THAL co-administration on serum creatinine and ZOL PK was investigated with a repeated measures analysis using a mixed model and paired t-tests. P < .05 was regarded as statistically significant. Results: 243 patients have been randomized (114 to receive THAL, 129 without). Analysis has been completed on 171 patients (79/92) who have received a median of 11 and 9 doses of ZOL respectively. 6 patients had ZOL withheld because of a rise in serum creatinine (2 treated with THAL, 4 treated without THAL). There were no significant differences in creatinine levels between patients treated with or without THAL, over time (P = .58), although a small increase in mean creatinine levels was noted over time in both arms at 0.64 mmol/L per 4 week cycle. PK was investigated in a total of 24 patients equally distributed among the treatment arms. No statistically significant influence was found of THAL co-administration on the PK parameters of ZOL. Conclusions: These results suggest that co-administration of THAL with ZOL does not result in an increased risk for nephrotoxicity. Serum PK of ZOL is not influenced by THAL. ZOL is safe and well tolerated in multiple myeloma patients when used in combination with THAL.

Evaluating results from the multiple myeloma subset of patients treated with denosumab or zoledronic acid (ZA) in a randomized phase III study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8589-8589 ◽  
Author(s):  
Noopur S. Raje ◽  
Wolfgang Willenbacher ◽  
Vania Hungria ◽  
Andrew Spencer ◽  
Yulia Alexeeva ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Solid Tumors ◽  
Primary Endpoint ◽  
Stem Cell Transplant ◽  
Phase Iii ◽  
Cell Transplant ◽  
Phase 3

8589 Background: Denosumab (dmab) is a fully human monoclonal antibody against RANKL and is superior to ZA in preventing skeletal-related events (SREs) as shown in 3 identically designed phase 3 trials (N=5723). Overall survival (OS) was balanced between treatment groups in the overall study populations of these trials. In the trial of patients (pts) with solid tumors (excluding breast and prostate) and multiple myeloma (MM), OS was longer for dmab pts with lung cancer, shorter for pts with MM, and balanced for pts with other solid tumors. This analysis further characterizes the results from the MM subset of this trial. Methods: Pts with solid tumors or MM were randomized (1:1) to receive 120 mg of SC dmab or 4 mg of IV ZA Q4W. Daily calcium and vit D supplements were strongly recommended. The primary endpoint was the time to first on-study SRE; results from the primary endpoint and lung cancer subset were previously reported. Results: Of 1776 randomized pts, 10% had MM (93 ZA, 87 dmab). OS favored ZA (hazard ratio: 2.26; 10 subject difference in deaths). 1-year OS was 83% dmab, 97% ZA. Imbalances in baseline prognostic characteristics were observed. More pts in the dmab arm had low baseline renal function (CrCl < 40 mL/min) (ZA 2 [2%], dmab 9 [10%]) and more ZA pts underwent stem cell transplant (ZA 23 [25%], dmab 15 [17%]). Additionally, more ZA pts had stage I tumors at diagnosis (ZA 13 [14%], dmab 9 [10%]) and better performance status (ECOG = 0; ZA 30 [32%], dmab 21 [24%]). Study discontinuations due to consent withdrawal or lost to follow-up were also higher in the ZA group (ZA 17 [18%], dmab 11 [13%]) and occurred earlier in the ZA arm (ZA 59%, dmab 45% within 9 months of randomization). Conclusions: In this SRE study of dmab vs ZA, pts were stratified by baseline characteristics known to affect SRE outcomes, but not by prognostic factors or concurrent anticancer therapy that may impact survival in MM. OS results in the MM cohort are difficult to interpret due to small sample size and imbalances in baseline disease characteristics, stem cell transplant therapy, and consent withdrawal or loss of follow-up that favored ZA. A phase 3 trial is currently underway, which controls for these factors in pts with MM. Clinical trial information: NCT00330759.

scholarly journals Phase II Study of the Combination of Interleukin-2 with Zoledronic Acid As Maintenance Therapy Following Autologous Stem Cell Transplant in Patients with Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5697-5697 ◽  
Author(s):  
Gabriele Buda ◽  
Rita Fazzi ◽  
Giovanni Carulli ◽  
Sara Galimberti ◽  
Paola Sammuri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Zoledronic Acid ◽  
Adverse Events ◽  
Maintenance Therapy ◽  
Residual Disease ◽  
Interleukin 2 ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Gamma Delta

Abstract Background: Multiple myeloma is still today an incurable disease. The many therapeutic techniques and new therapies proposed in recent years have extended survival but did not allow for healing. Further study allowed to demonstrate that a maintenance could be useful to control the progression of disease. However, there is no clear indication for which maintenance has to be used after a first line of induction therapy. The technique of allograft, used in patients at highest risk, demonstrates that the immune response to the residual disease plays a key role in the success of this technique. Among the major players in response to myeloma, in allogeneic stem cell transplantation, gamma delta lymphocytes play a significant action: complete response after allogeneic few months later (also the molecular level) happen in parallel with the presence in the bone marrow of a significant proportion of lymphocytes with gamma delta oligoclonal expression of TCR rearrangements. Zoledronic acid induces proliferation of these cells by the production of several cytokines, in particular interleukin-2 (IL-2). Furthermore, T lymphocytes Vdelta2 are proved to be crucial antineoplastic mediators and, after expansion in vitro, capable of controlling tumor growth in animal models. These data confirm the hypothesis that gammadelta lymphocytes have a role in controlling the growth of myeloma plasma cells and can be active on the residual disease after autologous stem cell transplant. We planned to evaluate the role of the association of Zoledronate and IL-2 in vivo as post ASCT maintenance therapy in patients with newly diagnosed multiple myeloma (NDMM). Methods: This is a single arm phase II multicenter ongoing study of the combination of IL-2 with zoledronic acid as maintenance therapy for NDMM patients post ASCT. The primary objective was to establish safety and efficacy of IL-2 as maintenance therapy. The secondary objective was to evaluate the immunological expansion of gamma delta lymphocytes. Eligible patients had undergone ASCT, with melphalan as a preparative regimen. At July 2016, forty two patients in very good partial remission (VGPR) have been enrolled in the study (total planned enrollment: 43 pts) and started maintenance therapy 90-180 days post ASCT. Maintenance schedule included IL2 and zoledronic acid. IL2 was administered at a fixed dose of 2 x 106UI from day 1 to day 7 for the first cycle and with the maximum tolerated dose (up to a max of 8 x 106UI) from day 1 to day 7 for subsequent cycles (dose escalation of 25% in each cycle in the absence of toxicity). Zoledronic acid was infused 4 mg iv on day 2. This dosing regimen is repeated every 28 days until disease progression. Adverse events were graded by NCI-CTCAE v4. Response was assessed by the modified International Uniform Response Criteria. Results and toxicity: 42 patients (pts) have been enrolled with a median age of 59 (range 42-72); 50% were male and 50% female. All the 42 pts have received a median of 11 cycles (range 1-23). Of the 42 pts 21 remain on therapy (data at July 2016), 21 pts are off study: 9 due to progressive disease (PD) and 12 due to consent withdrawal. Among the 9 pts with PD, the median PFS post ASCT was 12 months (2-18 months). Of the 42 pts, 33 (79%) not progressed after a median of 13 months (range 1-33) and the median PFS has not been reached. 7/42 patients (17%) reached complete remission. Peripheral and bone marrow analysis of gamma delta lymphocytes expansion to evaluate the level of immune response is still under examination. Grade 1/2 hematologic adverse events (AEs) included: grade 1 (G1) anemia (3 pts), G1 neutropenia (3). Grade 1/2 drug-related non-hematologic AEs included: G1 fever (25) G2 fever (8); G2 constitutional symptoms (joint pains) (20); G2 constipation (4); G1/2 nausea (10); G1 fatigue (15), G1/2 cutaneous rash (2). Conclusions: Long term administration of combination of IL-2/zoledronate as maintenance therapy post ASCT is feasible. The incidence of non hematologic adverse events (in particular fever) were manageable with no dose escalation of IL-2 over 5 x 106UI. This immunological approach, without any chemotherapeutic drug, seems to be able to control the disease and to obtain the complete remission in a subgroup of myeloma patients. Disclosures No relevant conflicts of interest to declare.

Pegylated Liposomal Doxorubicin (PLD) in Combination with Bortezomib (B) May Provide Therapeutic Advantage for High-Risk Multiple Myeloma Patients Relapsing within 12 Months of Stem Cell Transplant.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2730-2730
Author(s):  
Shaji Kumar ◽  
J. Blade ◽  
J. San Miguel ◽  
R. Hajek ◽  
A. Nagler ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Risk ◽  
Phase Iii ◽  
Late Relapse ◽  
Cell Transplant ◽  
Early Relapse ◽  
Therapeutic Advantage ◽  
Significant Difference ◽  
Relapse Group

Abstract Background: Patients (Pts) with multiple myeloma (MM) who relapse within 12 months of autologous stem cell transplantation (SCT) have a poor prognosis. As reported by Mahmood et al. (ASCO 2007), of 432 pts who received SCT at the Mayo Clinic between 1994–2005, those with early relapse within 12 months (94/432– 22%) showed poorer median overall survival. Kaplan-Meier estimates of 12-month survival from the date of first relapse were 37% for pts relapsing within 12 months after SCT as compared to 85% for those relapsing after 12 months. In that study, pts had received regimens other than B. In a recent report of a large, phase III study (DOXIL-MMY3001), the combination of PLD+B improved time to progression (TTP) as compared to B alone (Orlowski et al. JCO 2007). The present analysis examined the 12-month post-randomization survival of patients who had early (<12 months) vs. late (≥12 months) relapse following SCT, as well as the effect of PLD+B vs. B alone in pts who had relapsed early. Methods: This was a retrospective analysis of 646 pts who received intravenous B, 1.3 mg/m2 on days 1,4,8 and 11 of every 21-day cycle ± PLD, 30 mg/m2 on day 4. Results: 359 pts had previously received transplant, 114 (32%) of whom relapsed within 12 months from SCT. The median age, gender distribution, time from diagnosis trial enrollment, measures of disease burden (M-Protein levels and B2M) and renal function were comparable between the early and late relapse groups. There was no difference in overall response rates [complete + partial response (CR+PR)] or very good PR (VGPR) rates between the two groups, or between treatment arms within each group. There was no significant difference in TTP between early vs. late relapse groups (HR=0.94). 12-month survival from randomization was significantly lower in the early relapse group as compared to late relapse (83% vs. 92% respectively, p=0.009). However, within the early relapse group 12-months post-randomization survival rate was significantly superior following treatment with PLD+B as compared to B alone [52/56 patients (93%) vs. 43/58 patients (74%) respectively, p=0.01]. Correspondingly, TTP was better in this group with PLD+B vs. B alone (276 days vs. 205 days respectively, p=0.13). Overall, the toxicity profiles of the combination and B alone were comparable regardless of early or late relapse following SCT. Conclusions: The present analysis of the MMY3001 study corroborates the prior Mayo observation of lower survival in MM pts relapsing within 12 months of SCT. Importantly, it demonstrates that PLD+B may provide a therapeutic advantage for high-risk MM pts with early relapse following SCT.

scholarly journals Ixazomib as Postinduction Maintenance for Patients With Newly Diagnosed Multiple Myeloma Not Undergoing Autologous Stem Cell Transplantation: The Phase III TOURMALINE-MM4 Trial

2020 ◽  
Vol 38 (34) ◽  
pp. 4030-4041
Author(s):  
Meletios A. Dimopoulos ◽  
Ivan Špička ◽  
Hang Quach ◽  
Albert Oriol ◽  
Roman Hájek ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Primary Endpoint ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
To Receive

PURPOSE Maintenance therapy prolongs progression-free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) not undergoing autologous stem cell transplantation (ASCT) but has generally been limited to immunomodulatory agents. Other options that complement the induction regimen with favorable toxicity are needed. PATIENTS AND METHODS The phase III, double-blind, placebo-controlled TOURMALINE-MM4 study randomly assigned (3:2) patients with NDMM not undergoing ASCT who achieved better than or equal to partial response after 6-12 months of standard induction therapy to receive the oral proteasome inhibitor (PI) ixazomib or placebo on days 1, 8, and 15 of 28-day cycles as maintenance for 24 months. The primary endpoint was PFS since time of randomization. RESULTS Patients were randomly assigned to receive ixazomib (n = 425) or placebo (n = 281). TOURMALINE-MM4 met its primary endpoint with a 34.1% reduction in risk of progression or death with ixazomib versus placebo (median PFS since randomization, 17.4 v 9.4 months; hazard ratio [HR], 0.659; 95% CI, 0.542 to 0.801; P < .001; median follow-up, 21.1 months). Ixazomib significantly benefitted patients who achieved complete or very good partial response postinduction (median PFS, 25.6 v 12.9 months; HR, 0.586; P < .001). With ixazomib versus placebo, 36.6% versus 23.2% of patients had grade ≥ 3 treatment-emergent adverse events (TEAEs); 12.9% versus 8.0% discontinued treatment because of TEAEs. Common any-grade TEAEs included nausea (26.8% v 8.0%), vomiting (24.2% v 4.3%), and diarrhea (23.2% v 12.3%). There was no increase in new primary malignancies (5.2% v 6.2%); rates of on-study deaths were 2.6% versus 2.2%. CONCLUSION Ixazomib maintenance prolongs PFS with no unexpected toxicity in patients with NDMM not undergoing ASCT. To our knowledge, this is the first PI demonstrated in a randomized clinical trial to have single-agent efficacy for maintenance and is the first oral PI option in this patient population.

Endocrine Effects of Adjuvant Letrozole Compared With Tamoxifen in Hormone-Responsive Postmenopausal Patients With Early Breast Cancer: The HOBOE Trial

2009 ◽  
Vol 27 (19) ◽  
pp. 3192-3197 ◽  
Author(s):  
Emanuela Rossi ◽  
Alessandro Morabito ◽  
Francesca Di Rella ◽  
Giuseppe Esposito ◽  
Adriano Gravina ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Zoledronic Acid ◽  
Early Breast Cancer ◽  
Phase Iii ◽  
Endocrine Effects ◽  
Phase Iii Trial ◽  
Treatment Groups ◽  
To Receive ◽  
Ongoing Phase ◽  
Over Time

Purpose We compared the endocrine effects of 6 and 12 months of adjuvant letrozole versus tamoxifen in postmenopausal patients with hormone-responsive early breast cancer within an ongoing phase III trial. Patients and Methods Patients were randomly assigned to receive tamoxifen, letrozole, or letrozole plus zoledronic acid. Serum values of estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, dehydroepiandrosterone-sulphate (DHEA-S), progesterone, and cortisol were measured at baseline and after 6 and 12 months of treatment. For each hormone, changes from baseline at 6 and 12 months were compared between treatment groups, and differences over time for each group were analyzed. Results Hormonal data were available for 139 postmenopausal patients with a median age of 62 years, with 43 patients assigned to tamoxifen and 96 patients assigned to letrozole alone or combined with zoledronic acid. Baseline values were similar between the two groups for all hormones. Many significant changes were observed between drugs and for each drug over time. Namely, three hormones seemed significantly affected by one drug only: estradiol that decreased and progesterone that increased with letrozole and cortisol that increased with tamoxifen. Both drugs affected FSH (decreasing with tamoxifen and slightly increasing with letrozole), LH (decreasing more with tamoxifen than with letrozole), testosterone (slightly increasing with letrozole but not enough to differ from tamoxifen), and DHEA-S (increasing with both drugs but not differently between them). Zoledronic acid did not have significant impact on hormonal levels. Conclusion Adjuvant letrozole and tamoxifen result in significantly distinct endocrine effects. Such differences can explain the higher efficacy of letrozole as compared with tamoxifen.

scholarly journals Evaluating Factors Influencing Receipt of Stem Cell Transplant and Time to Transplant at a Diverse Metropolitan Transplant Center: Do Racial Disparities Persist?

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 323-323
Author(s):  
Harsh Shah ◽  
Seongho Kim ◽  
Scott Klimecki ◽  
Joseph P. Uberti ◽  
Charles A. Schiffer ◽  
...  
Keyword(s):  
Stem Cell ◽  
Racial Disparities ◽  
Selection Bias ◽  
Regression Models ◽  
Stem Cell Transplant ◽  
Multivariable Analysis ◽  
Cell Transplant ◽  
Public Insurance ◽  
To Receive ◽  
Over Time

Abstract Background: Prior studies have demonstrated disparities in the utilization of stem cell transplant (SCT) based on age, race, and insurance type. Whether delays to SCT occur as a result of these disparities is not well established. We evaluated whether we observed similar trends in a large metropolitan SCT center with a large population of minority patients (pts). Methods: We identified pts at Karmanos Cancer Institute who had their initial SCT consultation from 2009 - 2016, and evaluated pts who received or did not receive SCT for the diagnoses of acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplastic syndrome (MDS), multiple myeloma (MM), or non-Hodgkin lymphoma (NHL). The associations of SCT receipt status with 4 chosen predictors (age at the initial SCT consult (continuous variable), race [Caucasian vs. Non-Caucasian], sex, diagnosis [AML/ALL vs MDS vs. NHL vs MM]) were assessed by logistic regression models. Of those who received SCT, time to SCT was calculated from the date of coordinator intake (date of 1st SCT consult + screening initiated) to the date of SCT. Kaplan-Meier estimates were used to summarize the distributions of time to SCT. Cox proportional hazards regression models were fit to assess associations between 7 prespecified predictors (age, race, sex, diagnosis, type of SCT [Auto vs. Allo], county [Metro (three counties within Metro Detroit) vs. Non-Metro], and insurance [Private vs. Public (Medicaid, Medicare, others)] and time to SCT. Results: 2811 pts were included in our study, and of these 1644 received SCT. In multivariable analyses, non-Caucasian (n= 585 with 495 African-Americans) compared to Caucasian (n=2226) (OR 0.68, p<0.001, 95% CI 0.56-0.83), and NHL pts (n=750) compared to MM (n=1136) (OR 0.38, p<0.01, 95% CI 0.31-0.46) or AML/ALL(n=642) (OR 0.76, p=0.01, 95% CI 0.61-0.95) and older pts compared to younger (OR 0.97, p<0.001, 95% CI 0.97-0.98) were less likely to receive a SCT. There was an interaction of race with both age and diagnosis; therefore propensity match scoring analysis was performed to reduce selection bias due to these interactions (matching Caucasians and non-Caucasians by age and diagnosis), resulting in 1170 matched pts. Multivariable analysis among matched pts revealed that older compared to younger, non-Caucasian compared to Caucasian, and NHL pts compared to MM pts were less likely to receive SCT and remained independently significant. Interestingly, these differences in ORs of SCT between non-Caucasians and Caucasians depended on the year of initial consultation, and diminished over time (Fig 1). We then evaluated all pts who received SCT (n=1631). 1307 (80%) were Caucasian and 324 (20%) were non-Caucasian (273 were African-Americans). The median time to SCT was 3.24 months for all pts and 75% underwent transplantation by ~4.5 months. In the multivariable analysis, non-Caucasian (median 3.8 months) compared to Caucasian (median 3.28 months) (HR 0.75, p<0.01, 95% CI 0.65-0.85), public insurance (n=800, median 3.43 months) compared to private insurance (n=831, median 3.28 months) (HR 0.90, p=0.04, 95% CI 0.81-0.99), auto SCT (n= 983, median 3.51 months) compared to allo SCT (n= 648, median 3.1 months) (HR 0.82, p<0.05, 95% CI 0.67-0.99), and NHL pts (n=360, median 3.57 months) compared to AML/ALL pts (n=367, median 2.95 months) (HR 0.74, p<0.01, 95% CI 0.61-0.90) had significantly longer times to SCT. To reduce selection bias due to the association of race with age, county, type of SCT, insurance, and diagnosis, propensity matched scoring analysis was performed between races resulting in 624 matched pts. After matching, multivariable analysis still demonstrated that non-Caucasian and public insurance were independent factors in delay to SCT. However, differences in HRs of time to SCT between races depended on the year of consultation and improved over time (Fig 2). Conclusion: In this large retrospective analysis, we observed that race, age, and diagnosis are independent significant factors impacting receipt of SCT. Race and insurance status were independent factors associated with more prolonged time to SCT. Importantly, the effect of racial disparities in receipt of SCT and time to SCT are declining over time. Further analysis of the impact of social, medical, and financial factors are in progress. Disclosures No relevant conflicts of interest to declare.

Phase III Intergroup Study of Lenalidomide (CC-5013) Versus Placebo Maintenance Therapy Following Single Autologous Stem Cell Transplant for Multiple Myeloma (CALGB 100104): Initial Report of Patient Accrual and Adverse Events.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3416-3416 ◽  
Author(s):  
Philip L. McCarthy ◽  
Kouros Owzar ◽  
Edward A. Stadtmauer ◽  
Sergio Giralt ◽  
David D Hurd ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Maintenance Therapy ◽  
Research Funding ◽  
Progressive Disease ◽  
Study Drug ◽  
Phase Iii ◽  
Cell Transplant ◽  
Grade 5 ◽  
Grade 3

Abstract Abstract 3416 Poster Board III-304 Relapse and/or progression of disease are the primary causes of treatment failure after autologous hematopoietic stem cell transplant (ASCT) for multiple myeloma (MM). The primary objective of CALGB 100104 was to investigate whether adding maintenance therapy would improve the time to progression (TTP). The study was powered to detect an improvement of 9.6 months (prolongation of TTP from 24 months to 33.6 months) in MM patients undergoing a single ASCT. Secondary objectives were the Complete Response conversion rate following maintenance initiation, the Overall Survival and the feasibility of long term lenalidomide maintenance therapy. Eligible MM patients were Durie-Salmon Stage I-III patients within 1 year of diagnosis, receiving at least 2 months of any induction therapy with response (Stable Disease (SD) or better) and ≤ 70 years of age. Patients with progressive disease prior to ASCT were not eligible for study. Patients underwent stem cell mobilization followed by Melphalan 200 mg/m2 and ASCT with a minimum of 2 × 106 CD34 cells/kg for stem cell infusion. Responding patients with SD or better were randomized at day 100 to 110 post ASCT to study drug versus placebo. Patients with progressive disease were not randomized. Randomized patients were stratified by elevated β2 microglobulin at diagnosis and prior thalidomide or lenalidomide use during induction therapy. The starting dose was 10 mg daily with an escalation at 3 months to 15 mg if tolerated. Study drug could be de-escalated by 5 mg daily if not tolerated. Patients could be maintained at 5, 10 or 15 mg as tolerated and were followed with monthly complete blood counts. Drug was held for neutropenia (Absolute Neutrophil Count (ANC) < 500/μl or thrombocytopenia (<30,000/ μl) and restarted after resolution of cytopenia(s). Patients were re-staged by blood and urine testing every 3 months, by skeletal survey and bone marrow testing yearly and remained on maintenance therapy until progression. A total of 568 pts were registered at centers from the following cooperative groups: CALGB (n=377), ECOG (n=132), and BMT-CTN (n=59). The study opened in 12/2004 with increasing annual accrual: 2005, n=33, (6%); 2006, n=62, (11%); 2007, n=137, (24%); 2008, n=214, (38%); 2009, n=122, (21%) and study closure on 07/03/09. The drop out rate before randomization at day 100 to 110 was projected to be 10-15% with an expected randomization of 462 patients. Among the 568 registered patients, 424 have been randomized, 81 have dropped out pre-randomization and 63 are pending randomization as of 08/06/09. Projected final randomization is approximately 475. Pooled Hematologic and Non-Hematologic Adverse Events (AEs) are available from 275 patients in both arms. Individual patients experiencing Hematologic AEs are as follows: Grade 3 (severe) n=43 (16%); Grade 4 (life-threatening) n=26 (9%); and no Grade 5 (lethal). Individual patients experiencing Non-Hematologic AEs are as follows: Grade 3 n=74 (27%); Grade 4 n=9 (3%); Grade 5 n=5 (2%). The most common Non-Hematologic AEs were infection, fever, rash and fatigue. The Data Safety and Monitoring Board (DSMB) will continue to monitor the study for AEs and determination of progression. This large Phase III study has successfully completed patient registration and is nearing completion of patient randomization at day 100 to 110 post ASCT through the cooperation of the Intergroup oncology and transplant clinical research groups. Further analysis will determine if maintenance therapy with lenalidomide (CC-5013) is of benefit for MM patients following single ASCT. Disclosures McCarthy: Celgene: Speakers Bureau. Off Label Use: Lenalidomide for maintenance therapy following autotransplant for multiple myeloma. Stadtmauer:Celgene: Speakers Bureau. Richardson:Millenium (Research Funding and Advisory Board), Celgene, Keryx, BMS, Merck, Johnson and Johnson (All Advisory Board): Membership on an entity's Board of Directors or advisory committees, Research Funding. Anderson:Millenium: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding.

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