scholarly journals Long-term disease control in patients with newly diagnosed multiple myeloma after suspension of lenalidomide therapy

2014 ◽  
Vol 89 (3) ◽  
pp. 302-305 ◽  
Author(s):  
Taxiarchis V. Kourelis ◽  
Shaji K. Kumar ◽  
Geetika Srivastava ◽  
Morie A. Gertz ◽  
Martha Q. Lacy ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Control ◽  
Newly Diagnosed

Long Term Response To Lenalidomide With and Without Continuous Therapy Among Patients With Newly Diagnosed Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3209-3209
Author(s):  
Taxiarchis Kourelis ◽  
Shaji K Kumar ◽  
Geetika Srivastava ◽  
Morie A Gertz ◽  
Martha Q Lacy ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Control ◽  
Median Time ◽  
Research Funding ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Best Response ◽  
Standard Risk

Abstract Introduction Lenalidomide is an immunomodulatory drug that is active in newly diagnosed as well as relapsed multiple myeloma (MM). The goal of this study is to describe patients with newly diagnosed MM remaining on lenalidomide for more than 3 years (long term responders) as well as patients that after discontinuing lenalidomide were able to maintain disease control while only on observation (LenO group). Methods We retrospectively reviewed 283 patients with newly diagnosed MM that were treated with lenalidomide between January 2003 and January 2011. We excluded patients that underwent early autologous stem cell transplant (n=102) or had less than 3 years of follow-up (n=6), leaving 175 patients for the current analysis. Results Long term responders Thirty-three patients (19%) received lenalidomide for more than 3 years. When compared to patients receiving lenalidomide for less than 3 years, at baseline, long term responders were more likely to have standard risk disease (64% versus 44%, p=0.03) and less likely to have high risk disease (18% versus 4%, p=0.04). They were more likely to have achieved a deeper response (VGPR versus PR, p<0.001) and had a longer median time to best response (6 versus 4 months, p<0.001). When considering the 12 patients who received lenalidomide for more than 5 years, this group was more likely to have achieved a deeper response (CR versus PR, p<0.0001) and had a longer median time to achieving best response (9 versus 4 months, p<0.0001) than those 163 patients who remained on lenalidomide for fewer than 5 years. Observation group Thirty-three patients (19%) discontinued lenalidomide for reasons other than progression and were observed without receiving further treatment (LenO group). Prior to moving to observation, five patients had received lenalidomide for more than three years. Indications for stopping in the LenO group included: prolonged disease stability (n= 20); and toxicity (n=13). The only differences in baseline characteristics between the LenO group and patients that were not observed off any treatment was depth of response, with 61% (n=20) of LenO in VGPR or better versus 23% (n=23) in the remainder, p=0.0003. Median PFS from the time of discontinuing lenalidomide was significantly longer in those patients who took lenalidomide for more than 1 year (n=24) when compared to patients taking it for less than one year (n=9) (median PFS off therapy was 38.5 months versus, 14.9 months log rank 0.08; Wilcoxon p<0.05), figure 1a; PFS for those treated for 1-2 years (n=11) as compared to 2 years or greater (n= 13) were comparable to each other (data not shown). Among those taking lenalidomide for at least a year, PFS from time of discontinuing lenalidomide was superior in patients who had achieved a VGPR/CR (n=20) as compared to those who achieved only a PR (n=13) (Median 48.4 months versus 14.8 months, log-rank p<0.05; Wilcoxon p=0.01), figure 1b. Conclusion Approximately one out of five patients with newly diagnosed MM can achieve responses lasting more than three years while on treatment with lenalidomide. Patients with standard risk FISH and those achieving at least VGPR are more likely be long-term responders. Furthermore, long-term responders were more likely to be slow responders. We also demonstrate that suspension of lenalidomide therapy after 1 year among those patients achieving a VGPR or better can result in long-term disease control and can be considered as a therapeutic strategy. Disclosures: Kumar: Celgene: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Onyx: Consultancy, Research Funding. Gertz:Celgene: Honoraria. Lacy:Celgene: Honoraria. Dispenzieri:Celgene: Research dollars Other.

scholarly journals Clinical Impact of 18f-FDG PET/CT As a Valuable Prognostic Tool for the Newly Diagnosed Multiple Myeloma with Extramedullary Disease

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3142-3142
Author(s):  
Dong Won Baek ◽  
Hee Jeong Cho ◽  
Sang Kyun Sohn ◽  
Sung-Hoon Jung ◽  
Hong chae Moon ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Fdg Pet ◽  
Survival Outcomes ◽  
Newly Diagnosed ◽  
Prognostic Tool ◽  
Pet Ct ◽  
National University ◽  
18F Fdg ◽  
Fdg Pet Ct

Purpose 18F-FDG PET/CT (PET/CT) could be a valuable tool to predict long-term survival outcomes in patients with newly diagnosed multiple myeloma (MM). It has ability to distinguish metabolically active sites such as extramedullary disease (EMD) as well as bone damage with relatively high sensitivity and specificity. In this study, we attempted to evaluate the role of PET-CT as a novel prognostic tool for patients with newly diagnosed MM who have EMD. Patients and Methods This study included 211 patients who were newly diagnosed with multiple myeloma from Kyunpook National University Hospital and Chonnam National University Hwasun Hospital. We retrospectively analyzed the medical records of enrolled patients. PET/CT was performed at the diagnosis and EMD was identified in 36 patients (17.1%). Results With a median follow-up duration of 21.5 months (range 1.4-67.7), the estimated 2-year PFS and OS rates were 46.1% and 79.6%, respectively. The presence of PET/CT positive EMD and high maximum standardized uptake value (SUVmax) on baseline PET/CT were significantly associated with inferior long-term survivals in terms of PFS (p=0.013, p=0.007) and OS (p=0.002, p=0.004). In addition, patients who underwent autologous stem cell transplantation (auto-SCT) showed superior PFS (p=0.005) and OS (p=0.022) in PET/CT positive EMD group. Meanwhile, Revised-International Staging System (R-ISS) successfully predicted the prognosis in this study. When we modified R-ISS with the presence of EMD, survival outcomes of the R-ISS stage III patients who didn't have EMD were similar to R-ISS II, while patients with PET/CT positive EMD showed even worse prognosis than the R-ISS stage III group. In the multivariate survival analysis, the presence of EMD (hazard ratio (HR), 2.397; 95% confidence internal (CI), 1.281-4.483; p=0.006) and auto-SCT (HR, 0.326; 95% CI, 0.194-0.549; p<0.001) were related to PFS, while LDH (HR, 2.56; 95% CI, 1.221-5.366; p=0.013) level and auto-SCT (HR, 0.398; 95% CI, 0.167-0.953; p=0.039) were independent prognostic factors of OS. Conclusion In conclusion, PET/CT positive EMD was a poor prognostic factor in patients with newly diagnosed MM. In addition, PET/CT could be a valuable tool to make better risk-adapted treatment strategies with R-ISS in EMD positive MM patients. Above all, patients with PET/CT positive EMD should be considered auto-SCT to improve long-term survivals. Figure Disclosures No relevant conflicts of interest to declare.

scholarly journals BiRd (clarithromycin, lenalidomide, dexamethasone): an update on long-term lenalidomide therapy in previously untreated patients with multiple myeloma

Blood ◽  
2013 ◽  
Vol 121 (11) ◽  
pp. 1982-1985 ◽  
Author(s):  
Adriana Rossi ◽  
Tomer Mark ◽  
David Jayabalan ◽  
Paul Christos ◽  
Faiza Zafar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Second Primary ◽  
Newly Diagnosed ◽  
Key Points ◽  
Second Primary Malignancies

Key Points Long-term lenalidomide/dexamethasone/biaxin in newly diagnosed myeloma is safe and effective. No increased incidence of second primary malignancies seen in lenalidomide without alkylators.

scholarly journals Long-term survival with cyclophosphamide, bortezomib and dexamethasone induction therapy in patients with newly diagnosed multiple myeloma

2014 ◽  
Vol 167 (4) ◽  
pp. 563-565 ◽  
Author(s):  
Craig B. Reeder ◽  
Donna E. Reece ◽  
Vishal Kukreti ◽  
Joseph R. Mikhael ◽  
Christine Chen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Therapy ◽  
Newly Diagnosed ◽  
Term Survival ◽  
Long Term Survival

Multidimensional Flow Cytometric (MFC) Analysis of the Immune System of Multiple Myeloma (MM) Patients Achieving Long Term Disease Control

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 810-810
Author(s):  
Roberto J. Pessoa Magalhaes ◽  
María-Belén Vidriales ◽  
Bruno Paiva ◽  
Maria-Victoria Mateos ◽  
Norma C. Gutierrez ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Disease Control ◽  
B Cell ◽  
Nk Cells ◽  
Cell Populations ◽  
High Dose ◽  
Newly Diagnosed

Abstract Abstract 810FN2 Increasing evidence shows that a small fraction of MM patients (pts) treated with high-dose therapy followed by autologous stem cell transplantation achieve long-term remission. Interestingly, this is not restricted to pts in complete response (CR), since those that revert to a monoclonal gammopathy of undetermined significance (MGUS) profile may also achieve long-term remission, despite the persistence of residual myeloma plasma cells (PCs). These results suggest that in addition to the anti-myeloma therapy, other factors may play a role in the control of the disease. Herein, we used 8-color MFC for detailed characterization of the structural components of the immune system and hematopoietic precursor cells (HPC) in paired bone marrow (BM) and peripheral blood (PB) samples from 26 MM patients in long-term disease control (LTDC): 9 in continuous CR and 17 who reverted to an MGUS profile and that subsequently showed stable disease without treatment for ≥5 years (median of 9 years; range, 5–19). As controls, paired BM and PB samples from 23 newly-diagnosed MGUS and 16 MM pts, together with 10 healthy adults (HA), were studied in parallel. In all BM and PB samples the distribution of the major T- (CD4, CD8, Tregs and γδ), NK- (CD56dim and CD56bright) and B-cell subsets (Pro-B, Pre-B, naïve and memory), in addition to normal PCs, dendritic cell (DC) subsets (plasmacytoid, myeloid and monocytic), monocytes, and CD34+ HPC (myeloid and lymphoid), were studied. The percentage and absolute count of each cell population was analysed in the BM and PB, respectively. Comparison of the two groups of MM pts with LTDC (9 CR vs. 17 MGUS-like) showed similar (p>.05) cellular profiles in PB and BM, except for an increased number of BM and PB normal PCs in CR patients (P≤.04). Consequently, for all subsequent analyses, LTDC myeloma pts were pooled together. When compared to HA, patients with LTDC had increased numbers of CD8 T-cells and CD56dim NK-cells in both the BM and PB (p≤.03 and p≤.01, respectively). Despite this, the distribution of BM and PB CD4, CD8 and γδ T-cells among LTDC patients was similar (p>.05) to that of both newly-diagnosed MM and MGUS cases; in contrast, BM and PB Tregs were significantly decreased vs newly-diagnosed MM (P=.03) and MGUS (P=.04). Regarding B-cells and normal PCs, LTDC patients showed increased numbers of BM B-cell precursors (both Pro-B and Pre-B cells) and normal PCs vs. newly diagnosed MM (P≤.05), but not MGUS, together with increased numbers of naïve B-cells vs. both MM and MGUS pts (P≤.01); all such cell populations returned to levels similar (p>.05) to those of HA. As expected, this also included the number of CD34+ B-cell HPC which was increased among patients who achieved LTDC vs MM (p=.02), at levels similar (p>.05) to those of MGUS and HA. Regarding DC, LTDC patients showed normal DC numbers in PB (but with higher PB myeloid-DC numbers vs. MM; p=.02), in association with decreased numbers of plasmacytoid DC and increased monocytic-DC in the BM vs. HA (p≤.04). No differences were found for the numbers of BM and PB monocytes. In summary, here we investigated for the first time the immune cell profile of MM patients who achieve long-term disease control. Our results show that, as newly-diagnosed MM, patients that achieve long-term disease control also show increased numbers of cytotoxic T-cells and CD56dim NK-cells; however, in contrast to newly-diagnosed MM, among LTDC patients such increase is associated with lower numbers of T-regs and an almost complete recovery of the normal PC, B-cell precursor and naïve B-cell compartments both in BM and PB. Further investigations on the activation and functional status of these cell populations are warranted.MO (%)/SP (cels./μl)HA N= 10MGUS N= 23MM N= 16LTDC-MM N= 26T cells9.588110.6117313113711926    CD4+4.85004.6624^6*5085463    CD8+3.7∼216∼4.63865.32645.3431    TCR γδ.2426.3230.2428.3421    Treg.4137.4141^.54*38.3432NK cells.7∼87∼1.51982.11721.6212    CD56 dim.65∼79∼1.41922.21681.6202B cells2.81471.8104.97*68*1.9160    Pro B.11—.06—.02*—.07—    Pre B.6—.4—.08—.23—    Naive SP—80—57^—36*—118    Normal-PCS.18.9.11.7.008.72*.11.84DCs.3449.3653.6848.558    Monocytes2.22472.42853.43023.1315    m-DC SP—11—14—8*—12    MO-DC.11∼29.2036.434.2837    p-DC.2∼4.1.145.112.8.123.8CD34+.9∼1.46.61.1.261.4.431.4    Mie-HPC.8∼—.53—.26—.36—    Linfo-HPC.1—.07—.03*—.05—*p≤.05 LTDC vs MM: ^ p≤.05 LTDC vs MGUS; ∼ p≤.05 LTDC vs HA Disclosures: Paiva: Jansen-Cillag: Honoraria; Celgene: Honoraria. Martinez:Janssen: Honoraria; Celgene: Honoraria. Maiolino:Centocor Ortho Biotech Research & Development: Research Funding.

Effects of induction and maintenance plus long-term bisphosphonates on bone disease in patients with multiple myeloma: the Medical Research Council Myeloma IX Trial

Blood ◽  
2012 ◽  
Vol 119 (23) ◽  
pp. 5374-5383 ◽  
Author(s):  
Gareth J. Morgan ◽  
Faith E. Davies ◽  
Walter M. Gregory ◽  
Alex J. Szubert ◽  
Sue E. Bell ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Medical Research ◽  
Bone Disease ◽  
Research Council ◽  
Medical Research Council ◽  
Newly Diagnosed ◽  
Treatment Pathways ◽  
Skeletal Related Event ◽  
Oral Clodronate

AbstractThe Medical Research Council Myeloma IX Trial (ISRCTNG8454111) examined traditional and thalidomide-based induction and maintenance regimens and IV zoledronic acid (ZOL) and oral clodronate (CLO) in 1960 patients with newly diagnosed multiple myeloma. Overall survival (OS) and skeletal-related event (SRE) data have been reported for the overall trial population. The present analysis investigated optimal therapy regimens for different patient populations in Myeloma IX. Patients were assigned to intensive or nonintensive treatment pathways and randomized to induction cyclophosphamide, vincristine, doxorubicin, and dexamethasone (CVAD) versus cyclophosphamide, thalidomide, and dexamethasone (CTD; intensive) or melphalan and prednisolone versus attenuated oral CTD (CTDa; nonintensive). Patients were also randomized to ZOL or CLO. In the nonintensive pathway, CTDa produced better responses and lower SRE rates than melphalan and prednisolone. ZOL improved OS compared with CLO independently of sex, stage, or myeloma subtype, most profoundly in patients with baseline bone disease or other SREs. In patients treated for ≥ 2 years, ZOL improved OS compared with CLO from randomization (median not reached for either; P = .02) and also from first on-study disease progression (median, 34 months for ZOL vs 27 months for CLO; P = .03). Thalidomide-containing regimens had better efficacy than traditional regimens, and ZOL demonstrated greater benefits than CLO.

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