Improvement in Renal Function and Its Impact on Survival in Patients with Newly Diagnosed Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3368-3368
Author(s):  
Wilson I Gonsalves ◽  
Nelson Leung ◽  
S. Vincent Rajkumar ◽  
Angela Dispenzieri ◽  
Francis Buadi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
High Risk ◽  
Renal Impairment ◽  
Induction Therapy ◽  
Response To Therapy ◽  
Older Age ◽  
Newly Diagnosed ◽  
Renal Response ◽  
Novel Agent

Abstract Background: Renal impairment is a common feature of multiple myeloma (MM) seen in over a quarter of newly diagnosed patients (pts). Studies have confirmed the presence of renal impairment (RI) as a strong predictor of inferior survival in MM. Some studies have also indicated that reversibility of RI is associated with improved survival. However, it is not clear if normalization of renal function improves the outcome to that expected for MM pts without RI at diagnosis. Methods: We evaluated 1,135 consecutive pts with newly diagnosed MM seen at the Mayo Clinic, Rochester between December 2002 and January 2011. Renal function was assessed by the estimated creatinine clearance (CrCl) which was calculated by the modified MDRD formula. We examined these pts for improvement in renal function based on their CrCl at diagnosis and their highest CrCl during their disease course. RI was defined as having a CrCl of < 60. Pts were categorized based on their renal function at diagnosis and response to therapy: Group 1- CrCl >60 at diagnosis, Group 2- CrCl <60 at diagnosis but improved to >60 after therapy and Group 3- CrCl <60 at diagnosis and remained <60 after therapy. The degree of restoration of renal function was evaluated according to the IMWG criteria. Survival analysis was performed by the Kaplan-Meier method and differences assessed using the log rank test. Results: The median age at diagnosis was 65 years (range; 22 - 93) and 682 (60%) were male. The median follow up for the entire group from diagnosis was 73 mos (95% CI; 69 - 77). At diagnosis, 123 (11%) pts had a CrCl < 30, 322 (28%) had a CrCl of 30-59 and 690 (61%) had a CrCl >60. Most pts (N=754, 67%) received novel agent induction (NAI) therapy. The median PCLI was 0.7 (range: 0 – 22) and 91 (21%) pts had high-risk cytogenetics by FISH. The median OS for the pts with CrCl at diagnosis of < 30, 30-59 and >60 were 41 mos, 60 mos and not reached respectively (P < 0.001). Of the 445 patients with RI, the median absolute creatinine and CrCl at diagnosis were 1.6 mg/dL (range: 1 – 11) and 44 (range: 4 – 59) respectively. Among pts with RI, any improvement in CrCl was seen in 295 (66%) with median time to highest CrCl of 5 months and 228 (51%) had complete reversal of their RI. The median OS for pts with RI at diagnosis receiving and not receiving NAI therapy was not reached (NR) vs. 46 mos (P < 0.001). The median OS for Groups 1, 2 and 3 were NR, 60 and 49 mos respectively (Figure 1, P < 0.001). At a 6 month landmark analysis, the median OS for Groups 1, 2 and 3 were NR, 67 and 62 mos respectively (P < 0.001). The complete renal response and no renal response rates for pts with RI at diagnosis receiving and not receiving NAI induction therapy was (57% vs. 44%, P=0.004) and (29% vs. 39%, P=0.04) respectively. In a univariable analysis, presence of RI at diagnosis, no NAI therapy, older age, ISS stage 3, high-risk FISH, elevated PCLI, diagnosis prior to 2007 and increased LDH were found to predict for worse OS; however only older age (P<0.001), high-risk FISH (P=0.037) and lack of NAI therapy (P=0.023) retained their negative prognostic significance in a multivariable analysis. Conclusion: MM pts with RI treated with novel agent induction therapy demonstrate improved responses in their renal function and OS. The results also demonstrate improved outcome for pts with improvement in renal function, but it remains inferior to pts with normal renal function at diagnosis. These results have implications for early treatment strategies for pts at risk of developing renal insufficiency. Figure 1: OS based on improvement in CrCl upon receiving treatment Figure 1:. OS based on improvement in CrCl upon receiving treatment Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Reversibility of Renal Failure in Newly Diagnosed Patients with Multiple Myeloma and the Role of Novel Agents.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 955-955 ◽  
Author(s):  
Maria Roussou ◽  
Efstathios Kastritis ◽  
Dimitrios Christoulas ◽  
Magdalini Migkou ◽  
Maria Gavriatopoulou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Renal Impairment ◽  
High Dose ◽  
Newly Diagnosed ◽  
Agent Based ◽  
Renal Response ◽  
Group A ◽  
Group B ◽  
Novel Agent

Abstract Abstract 955 Renal impairment (RI) is a common complication of multiple myeloma (MM) and is associated with increased mortality. High dose dexamethasone-based regimens have been extensively used for the initial management of patients with MM presenting with RI. Recently, novel agent-based regimens have been introduced in the frontline management of MM. The purpose of our analysis was to assess the effect of novel agent-based regimens on the rate of RI improvement and compare their efficacy with conventional chemotherapy (CC) plus dexamethasone (Dexa) in newly diagnosed MM patients. Over the last decade, 82 patients with newly diagnosed MM and RI, defined as creatinine clearance (CrCI) <50ml/min, received frontline treatment in our Center. Patients were divided into three groups: group A: 28 patients who received CC plus Dexa-based regimens (VAD, VAD-like regimens, melphalan plus Dexa); group B: 38 patients who received IMiDs-based regimens (thalidomide or lenalidomide with high dose Dexa and/or cyclophosphamide or melphalan) and group C: 16 patients who received bortezomib-based regimens with Dexa. Renal complete response (RCR) was defined as a sustained increase of baseline CrCI to >60ml/min. Renal partial response (RPR) was defined as an increase of CrCI from<15 to 30-50ml/min. Renal minor response (RMR) was defined as sustained improvement of baseline CrCI of<15ml/min to 15-29 ml/min, or, if baseline CrCI was 15-29 ml/min, improvement to 30-59 ml/min. Patients in group B were older than those of groups A and C (p=0.01) while more patient in group C had light chain only MM than in groups A and B (p=0.04). There were no significant differences in the severity of RI, Bence Jones proteinuria, hypercalcemia or ISS stage among the three groups. Improvement of renal function, recorded as RMR or better, was achieved more frequently in patients treated with novel agents (group B: 87% and in group C: 94%) than in patients treated with CC plus Dexa-based regimens (64%, p=0.024). Among 9 patients who required renal dialysis 3 became independent of this procedure after treatment. We subsequently focused our analysis in major renal responses (RPR or RCR), because this endpoint is clinically more relevant. RCR was achieved in 43% of patients in group A, in 50% in group B and in 69% of patients in group C (p=0.2) and RCR+RPR rates were 50% and 57% and 81% for groups A, B and C respectively (p=0.1). Creatinine clearance <30 ml/min was associated with a significantly lower probability of RCR or RPR only in patients treated with CC plus Dexa- or with IMiDs-based regimens (p<0.01), but not in patients treated with bortezomib (p=0.529). The probability of RPR+RCR was similar for patients treated with IMiDs compared to CC plus Dexa-based regimens (p=0.619). In multivariate analysis bortezomib–based regimens (p=0.02, OR: 7, 95% CI 1.5-25) and CrCl>30 ml/min (p=0.002, OR: 6.1, 95% CI 2.5-22.5) were independently associated with a higher probability of RCR+RPR. The median time to RPR was similar for patients treated with IMiDs compared to CC plus Dexa-based regimens (2.2 months for Group A, 1.5 months for Group B, p=0.587) but it was significantly shorter for Group C (0.7 months, p=0.017). Other factors associated with a shorter time to ≥RPR included CrCl>30 ml/min (p=0.039) and age<75 (p=0.089). In multivariate analysis bortezomib–based regimens (p=0.004, OR: 3 95% CI 1.6-6.7) and CrCl>30 ml/min (p=0.006, OR: 2.5 95% CI 1.3-4.5) were independently associated with a shorter time to ≥RPR. In landmark analysis (time was one month in order to reduce bias due to early deaths), rapid improvement of renal function (≤1 month) was associated with a trend for a longer survival compared to patients who achieved renal response later (>1 month) (47 vs. 21 months, p=0.19). Myeloma response to treatment was 58%, 68% and 79% for the three treatment groups respectively and was associated with renal response (p=0.024), though less strongly with a major renal response (p=0.061). Our data indicate that novel agent-based regimens can improve renal function in most patients; furthermore bortezomib-based regimens improve renal function to a higher degree and significantly more rapidly than CC plus Dexa-based or IMiD-based regimens even in patients with severe renal impairment. We conclude that bortezomib-based regimens may be the preferred treatment for newly diagnosed myeloma patients who present with renal impairment. Disclosures: Dimopoulos: JANSSEN-CILAG: Honoraria; CELGENE: Honoraria.

The Role of Novel Agents on Reversibility of Renal Impairment in Newly Diagnosed Patients with Multiple Myeloma; a Single Center Experience on 112 Patients,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3961-3961
Author(s):  
Meletios A Dimopoulos ◽  
Maria Roussou ◽  
Maria Gkotzamanidou ◽  
Erasmia Psimenou ◽  
Despoina Mparmparoussi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Multivariate Analysis ◽  
Renal Impairment ◽  
Median Time ◽  
Novel Agents ◽  
Newly Diagnosed ◽  
Renal Response ◽  
Group B

Abstract Abstract 3961 Renal impairment (RI) is a frequent complication of multiple myeloma (MM). Proteasome inhibitors and immunomodulatory drugs (IMiDs) are used as frontline therapy for MM but their effect on renal function recovery has not been clearly defined. To address this issue we studied 112 patients with newly diagnosed MM and RI who were treated in the Department of Clinical Therapeutics of the University of Athens, over the last decade. RI was defined as an estimated glomelural filtration rate (eGFR) ≤60 ml/min, using the simplified MDRD formula. Patients were divided into three groups; group T included 53 patients who received thalidomide-based regimens (with dexamethasone alone, with dexamethasone and melphalan or cyclophosphamide, or with VAD); group B included 30 patients who received bortezomib-based regimens (with dexamethasone alone, with dexamethasone and thalidomide or with cyclophosphamide) and group L included 29 patients who received lenalidomide-based regimens (with dexamethasone or with melphalan and prednisone). Lenalidomide dose was adjusted for the degree of RI according to current recommendations. Renal complete response (CRrenal) was defined as a sustained increase of baseline eGFR to >60 ml/min, renal partial response (PRrenal) as an increase of eGFR from <15 to 30–50 ml/min and renal minor response (MRrenal) as sustained improvement of baseline eGFR of <15 ml/min to 15–29 ml/min, or, if baseline eGFR was 15–29 ml/min, improvement to 30–59 ml/min. Patients in groups T and L were older than those of group B (p=0.0001). Anemia (Hb <10 g/dl) was more frequent in patients of group L (p=0.007). There were no significant differences in the severity of RI, or other clinical and laboratory parameters among the three groups. An improvement of renal function, recorded as MRrenal or better, was achieved more frequently in patients treated with bortezomib-(83%) or thalidomide-based regimens (77%) than in patients treated with lenalidomide-based regimens (55%, p=0.033). We subsequently focused our analysis in major renal responses (at least PRrenal) since this endpoint is clinically more relevant. CRrenal was achieved in 53% of patients in group T, in 70% in group B and in 34% in group L (p=0.014), while CRrenal+PRrenal rates were 55%, 80% and 38% for groups T, B and L, respectively (p=0.004). eGFR <30 ml/min was associated with a significantly lower probability of at least PRrenal (p=0.016). In multivariate analysis bortezomib-based regimens (OR: 8.8, 95% CI: 2–37, p=0.003) and thalidomide-based regimens (OR: 2.85, 95% CI: 1.01–8, p=0.046) were associated with higher probability at least PRrenal than lenalidomide-based regimens. Other factors that were independently associated with higher probability of at least PRrenal, were baseline eGFR >30 ml/min (OR: 4.85, 95% CI: 1.9–12.5, p=0.001) and age ≤65 years (OR: 3.8, 95% CI: 1.07–13.5, p=0.038). The median time to first renal response was longer for patients of group L compared to those of group T (5.5 months vs. 1.5 months, p=0.038) and it was significantly shorter for patients of group B (0.85 months, p=0.001). The median time to major renal response was 1.1 months for bortezomib-based and 2.7 months for thalidomide-based regimens, and exceeds 6 months for lenalidomide-based regimens (p=0.002). In multivariate analysis bortezomib-based regimens (OR: 3.12, 95% CI: 1.35–7.2, p=0.008) and baseline eGFR >30 ml/min (OR: 1.93, 95% CI: 1.13–3.3, p=0.015) were independently associated with a shorter time to ≥PRrenal. Myeloma response to treatment was 61%, 83% and 83% for the three treatment groups, respectively and was associated with any renal response (≥MRrenal; p=0.008) and with a major renal response (CRrenal+PRrenal; p=0.001). Among 8 patients who required dialysis (group T 4 patients, group B 4 patients), 4 patients (2 in each group) became independent of this procedure. This is the first analysis which compared the role of the three novel agents in MM patients presenting with RI. Our data indicate that novel agent-based regimens can improve renal function in the majority of patients with RI. However, bortezomib- and thalidomide-based regimens are more efficacious than lenalidomide-based regimens in this setting. Furthermore, bortezomib-based regimens act more rapidly than IMiD-based regimens even in patients with severe RI. We conclude that bortezomib-based regimens are the preferred therapy for newly diagnosed myeloma patients with RI. Disclosures: Dimopoulos: Janssen-Cilag: Honoraria; Celgene: Honoraria; Millenium: Honoraria. Terpos:Janssen-Cilag: Honoraria; Celgene: Honoraria.

Reversibility of Renal Impairment of Multiple Myeloma Patients Treated with Bortezomib-Based Regimens: Identification of Predictive Factors.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1725-1725 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Maria Roussou ◽  
Efstathios Kastritis ◽  
Maria Gavriatopoulou ◽  
Flora Zagouri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Renal Function ◽  
Partial Response ◽  
Renal Impairment ◽  
Creatinine Clearance ◽  
Light Chain ◽  
Management Problem ◽  
Newly Diagnosed ◽  
Renal Response

Abstract Renal impairment (RI) is a frequent complication of multiple myeloma (MM) and a major management problem. Previous studies have shown that bortezomib is active and well tolerated in MM patients with RI and can be associated with improvement of renal function. The purpose of our analysis was to identify factors that may predict for renal impairment reversal in patients treated with bortezomib-based regimens. Over the last 5 years, 149 either newly diagnosed or relapsed/refractory MM patients received bortezomib-based regimens in our center. Our analysis is based on 46 consecutive patients with newly diagnosed (n=10) or relapsed/refractory (n=36) MM who presented with RI defined as creatinine clearance (CrCl) &lt; 50 mL/min. Median CrCl was 23 mL/min (range 6 to 48), 34 (74%) had a CrCl&lt;30 ml/min and 9 patients required renal dialysis. Sixteen patients (35%) had light chain only myeloma, elevated LDH&gt;300 IU/L was found in 24%, more than 2 gr/day of Bence Jones protein in 20 (44%) and kappa to lambda free light chain ratio was ≥8 or ≤0.125 in 25%. Patients received bortezomib (B) at standard dose and schedule, plus dexamethasone (D) (16 patients, 35%), or BD in combination with other agents such as thalidomide, doxorubicin or melphalan (30 patients, 65%). Renal complete response (RCR) was defined as a sustained increase of CrCl to &gt;60 mL/min after treatment. Renal partial response (RPR) was defined as an increase of CrCl by 50% and with improvement of renal function by at least one stage (stage IV: &lt;30 mL/min, stage III 30–59 mL/min) but with a post treatment CrCl &lt; 60 mL/min. RCR was documented in 22% of patients and RPR in 22% of patients. Thus, renal response (RCR + RPR) occurred in 20 patients (44%). The median time to renal response was 11 days (range 8 to 41). Among 9 patients who required dialysis 2 patients became independent of this procedure after the second cycle of treatment. The objective response rate (at least partial response) of the myeloma was 63%. Toxicities were similar to those seen in myeloma patients without renal failure who were treated with bortezomib-based regimens. Previously untreated patients (80% vs 33% for pretreated patients, p=0.012) and those with light chain only myeloma (69% vs 30%, p=0.012) had a higher probability to achieve renal response. Response of MM to treatment was also associated with higher rate of renal response (55% vs. 24% for non-responders, p=0.037). Creatinine clearance &lt;30 ml/min (47% vs. 33% for ClCr 330 ml/min, p=0.410), age&gt;75 years (p=0.309), corrected serum calcium ≥10,5 mg/dl (p=0.428), Bence Jones proteinuria ≥2g/day (p=0.167) or type of bortezomib regimen (BD or BD plus other agents, p=0.222) did not significantly affect the probability of renal response. Seventeen percent of patients presenting with RI died within the first 3 months after initiation of treatment. Patients with renal response had a trend for longer survival compared to those who did not achieve a renal response (79% vs 54% alive at 1 year, p=0.150). We conclude that when bortezomib-based regimens are administered to MM patients with RI, they are associated with a clinically meaningful renal response in 44% of them. Renal response is very rapid and occurred within 2 months in all patients. Previously untreated patients and those with light chain only myeloma may have a higher probability of renal response. Moreover, patients who achieved at least a partial response of their myeloma reversed RI more frequently than non-responders. Our data were derived from an unselected patient population with severe renal failure in more than two-thirds and with 20% of patients on dialysis. They provide further evidence that bortezomib-based regimens have a unique role in patients with RI.

Impact of lenalidomide-bortezomib-dexamethasone (RVd) induction on patients with newly diagnosed multiple myeloma and renal impairment: Results from the Connect MM Registry.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8518-8518
Author(s):  
Sikander Ailawadhi ◽  
Hans Chulhee Lee ◽  
Jim Omel ◽  
Kathleen Toomey ◽  
James W. Hardin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Renal Impairment ◽  
Progression Free Survival ◽  
Induction Treatment ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Front Line ◽  
Real World Data ◽  
The Impact

8518 Background: Patients (pts) with newly diagnosed multiple myeloma (NDMM) and renal impairment (RI) are often excluded from clinical trials. Data are limited on the effects of induction treatment in these pts, who may also be ineligible for autologous stem cell transplant (SCT) due to severity of RI. This analysis investigated the impact of RVd induction on renal function in transplant eligible (TE) and noneligible (TNE) pts from the Connect MM Registry, a US, multicenter, prospective, observational study. Methods: Eligible pts were ≥ 18 y and had symptomatic MM diagnosed ≤ 2 mos prior to enrollment, as defined by the International Myeloma Working Group criteria. For this analysis, pts that received front-line RVd for ≥ 3 cycles were grouped per transplant eligibility and renal function at baseline (BL; creatinine clearance [CrCl] < 30, 30-50, > 50-80, and > 80). Pts with progressive disease at BL were excluded. Renal function at 3 mos was measured. Median unadjusted progression-free survival (PFS) was calculated from start of regimen in TE and TNE populations, with pts grouped by CrCl (≤ 60 or > 60) at BL. Results: As of 7/23/19, 421 TE and 212 TNE pts received RVd for ≥ 3 cycles. TE and TNE pts were grouped by BL CrCl of < 30 (20 and 16 pts), 30-50 (36 and 50 pts), > 50-80 (117 and 63 pts), and > 80 (248 and 83 pts). Renal function improvement was observed in all pts receiving RVd, including those with moderate (30-50 CrCl) and severe (< 30 CrCl) RI at BL (Table). In pts with > 60 CrCl and ≤ 60 CrCl at BL, median PFS in TE pts was 48.6 mos and 43.2 mos, respectively. In TNE pts, median PFS was 36.4 mos and 30.6 mos, respectively. Conclusions: The results from the Connect MM Registry indicate that pts with NDMM and RI (including moderate and severe) who receive front-line RVd for ≥ 3 cycles may see improvement in renal function at 3 mos, regardless of transplant eligibility. RVd therefore can potentially be used in pts with RI. This analysis provides real-world data that support further investigation of RVd treatment in pts with moderate or severe RI. Clinical trial information: NCT01081028 . [Table: see text]

Real-World Renal Function Among Patients with Multiple Myeloma in the United States

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-30
Author(s):  
Joseph Mikhael ◽  
Erin Singh ◽  
Megan Rice
Keyword(s):  
United States ◽  
Multiple Myeloma ◽  
Renal Function ◽  
Combination Therapy ◽  
Renal Impairment ◽  
Drug Class ◽  
The United States ◽  
Second Line ◽  
Renal Response ◽  
Treatment Line

Background Multiple myeloma (MM) is the second most common hematologic malignancy and is associated with significant patient burden. Renal impairment has been shown to affect up to 50% of patients (pts) with MM. Renal impairment is an independent predictor of poor survival outcomes for pts with MM, with a median survival of approximately half that of pts without renal impairment. Aims To assess change in renal function by treatment line and drug class among pts with MM and renal impairment (defined as eGFR &lt;50 mL/min/1.73 m2 using the Modification of Diet in Renal Disease equation [eGFR-MDRD]), and to assess real-world outcomes by baseline renal status, renal response, and drug class. Methods Using the nationwide Flatiron Health EHR-derived de-identified database based in the United States, we identified MM pts diagnosed and treated between January 2011 and November 2019 who received ≥1 line of MM therapy and had information on race. We assessed the distribution of pts by eGFR-MDRD level at the start of the first and second line of therapy and the distribution of therapy use (ie, proteasome inhibitor [PI], immunomodulatory drug [IMiD], monoclonal antibody [mAb]). We also evaluated overall survival (OS) by treatment line, stratified by eGFR at the start of each treatment line. Complete renal response (CRR) was assessed in pts with eGFR-MDRD &lt;50 mL/min/1.73 m2; using International Myeloma Working Group recommendations, responders were defined as pts with ≥1 eGFR measurement ≥60 mL/min/1.73 m2 during the treatment line. Logistic regression models were used to examine the association between treatment class and complete renal responder status adjusted for other treatment classes received, age, sex, race, practice type, year of therapy line, and cytogenetic risk. Cox proportional hazard models were used to examine OS by treatment and renal response, adjusted for other treatment classes received, age, sex, race, practice type, year of therapy line, and cytogenetic risk. Flatiron Health, Inc., did not participate in the analysis of this data. Results For the 6990 pts included in the analysis, the mean age at start of initial therapy was 68 years, 46% were female, and 17% were Black. At start of treatment lines 1 and 2, approximately 25% had eGFR-MDRD &lt;50 mL/min/1.73 m2. At treatment initiation, pts with renal impairment were older (71 vs 67 years) and were more likely to present with ISS stage III at diagnosis (38% vs 10%). Pts with renal impairment at the start of each treatment line exhibited decreased OS. Among pts with renal impairment, pts with PI use in first (adjusted odds ratio [aOR] 1.36; 95% CI, 1.04-1.77) or second line (aOR 2.09; 95% CI, 1.38-3.16) were significantly more likely to have a CRR than those without PI use. Pts with IMiD use in first (aOR 2.14; 95% CI, 1.68-2.72) and second (aOR 1.61; 95% CI, 1.10-2.36) line were significantly more likely to have a CRR than those without IMiD use. When classified by both PI and IMiD use, pts with both PI and IMiD use were significantly more likely to have a CRR than those without use of either in the first (aOR 2.35; 95% CI, 1.54-3.60) and second line (aOR 3.89; 95% CI, 1.71-8.86). Pts with PI and IMiD use as well as a CRR also had greater OS in the first (adjusted hazard ratio [aHR] 0.52; 95% CI, 0.37-0.73) and second line (aHR 0.53; 95% CI, 0.32-0.88) vs pts without either PI or IMiD use and no CRR. The use of available mAbs in line 1 or line 2 was not significantly associated with renal response. Lower mAb use, especially in earlier treatment lines, prevented further analyses by mAb combination therapies. Conclusion In this study, MM pts with renal impairment were more likely to be older and to present with ISS stage III at diagnosis. Pts with decreased renal function exhibited decreased OS compared with non-renally impaired pts. Pts who were treated with combination therapy that included PIs and IMiDs together in early treatment lines were more likely to have a CRR and OS was prolonged among these pts, highlighting the benefits of combination therapy. These data suggest that treatment inducing a renal response may result in improved outcomes. Future investigations with larger datasets may improve the understanding of the prognostic value of renal impairment and optimal combination treatment regimens for these pts. Disclosures Mikhael: Amgen, Celgene, GSK, Janssen, Karyopharm, Sanofi, Takeda: Honoraria. Singh:Sanofi-Genzyme: Current Employment. Rice:Sanofi: Current Employment.

Recovery of Renal Function and Independence from Dialysis in Newly Diagnosed and Relapsed Multiple Myeloma Patients - A Single Instituition Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4847-4847
Author(s):  
Girish Ravindranathan ◽  
Tanya Indrakumar ◽  
Sohail Ahmad ◽  
Moez Dungarwalla ◽  
Pamela Kanagasabapathy ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Renal Function ◽  
Renal Impairment ◽  
Current Therapy ◽  
High Dose ◽  
Newly Diagnosed ◽  
Female Ratio ◽  
Male To Female ◽  
Relapsed Myeloma

Abstract Background: Renal impairment occurs in up to 30% of patients who present with multiple myeloma and in up tp 50% of patients at some stage of the illness. It is known that renal impairment can be reversed in a significant number of such patients by correction of precipitating factors and rehydration but that 3–12% patients will require dialysis or other major intervention. These patient have a worse prognosis largely due to an excess of early deaths, renal failure being the major cause of death in 14% of myeloma patients and contributing factor in a further 14%. (Drayson et al UK MRC MM trials 1980–2002) We have conducted a study to look into the clinical course and outcome of all patients with renal impairment sufficiently severe to be referred to the regional renal unit in South East England between 2000 and 2007 with either newly diagnosed multiple myeloma (MM) or relapsed disease to try to identify features which predict for better outcomes. Methods: 62 patients with MM and renal failure received treatment in our hospital over the last 8 years. Patients have been assessed for recovery of renal function and dialysis independence in two groups - newly diagnosed (n=47) and relapsed patients (n=15). They were analysed separately as the disease tends to be biologically different at presentation and relapse, and therapeutic options may be different. In addition relatively little data on relapsed myeloma with renal failure is available. Results: 14 patients in the newly diagnosed group and 4 in the relapsed group were deemed unsuitable for an active treatment approach and have been excluded from statistical analysis in this paper but will be analysed separately to try to identify factors which could improve the outcome for this group. The patients with newly diagnosed MM and actively treated had a mean age of 65.3±1.7 years (range 41.9–83.3), male to female ratio of 1.7:1 and a mean peak creatinine at presentation of 684.5±60.9 mmol/l (range 107–1820). Light chain myeloma was overrepresented and was seen in 57.5% of patients (n=19). 12 (36.3%) of 33 the new patients avoided dialysis. 21 required dialysis, of whom 8 patients (38.1%) recovered function to dialysis independence at 6 months. There were only 3 deaths at 6 months follow-up. The mean age of the relapsed patients was 61.8±3.5 years (range 34.9–80.7), male to female ratio of 2.6:1 and a mean peak creatinine at presentation of 824±118.4 mmol/l (range 231–1591). Majority of myeloma was IgA in 36.3% (n = 4). Among the 11 relapsed, 82% (n=9) required dialysis but a significant proportion, 88% (n=8), were dialysis independent at 6 months There was only one death within 6 months of a relapse. Treatments in the 2 groups varied but involved the use of regimes containing high dose steroids in most patients. Conclusions: Our data suggest that renal failure and dialysis dependence can be avoided or is reversible in a large number of newly diagnosed and relapsed myeloma patients. This study of an unselected group of patients receiving current therapy provides an important baseline against which to compare the effect of approaches involving the newer biological agents.

Lenalidomide and Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma; Dosing of Lenalidomide According to Renal Function and Effect On Renal Impairment.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3871-3871
Author(s):  
Meletios A. Dimopoulos ◽  
Dimitrios Christoulas ◽  
Maria Roussou ◽  
Efstathios Kastritis ◽  
Magdalini Migkou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Renal Impairment ◽  
Performance Status ◽  
Prior Treatment ◽  
Renal Response ◽  
Refractory Multiple Myeloma ◽  
Dvt Prophylaxis ◽  
Grade 3 ◽  
Abnormal Renal Function

Abstract Abstract 3871 Poster Board III-807 Lenalidomide and dexamethasone (RD) is an active regimen for the management of relapsed and/or refractory multiple myeloma (MM). Over the last 2 years consecutive patients with pre-existing peripheral neuropathy grade ≥ 2 were treated with RD, regardless of their performance status and renal function. Patients with disease refractory to thalidomide, bortezomib and dexamethasone (i.e. progressive disease during treatment or within 60 days of treatment completion) were also included. Lenalidomide was administered on days 1 to 21 according to creatinine clearance (CrCl): 25 mg/day for CrCl >50 ml/min, 10mg/day for CrCl 30-50 ml/min, 15 mg every other day for CrCl 15-30 ml/min and for patients on dialysis, 15 mg three times per week on the day after dialysis. Dexamethasone was administered at a dose of 40mg PO on days 1 to 4 and 15 to 18 for the first 4 cycles and only on days 1 to 4 thereafter. RD was repeated every 28 days till disease progression or unacceptable toxicity. All patients received DVT prophylaxis with aspirin 100 mg/day unless there were already on coumadin or LMWH for pre-existing DVT or for other indications, usually atrial fibrillation. So far, 46 patients have been included and their characteristics were: median age was 69 years (range 43-87 years); median lines of prior therapy were 3 (range 1-6); prior treatment with thalidomide-containing regimens: 74% of patients (thalidomide-refractory: 68% of patients); prior treatment with bortezomib-containing regimens: 78% of patients (bortezomib-refractory: 56%); dexamethasone-refractory: 61% of patients; performance status ≥2: 33% of patients; LDH >300 IU/dl (normal value >225 IU/dl): 13% of patients; extramedullary involvement: 9% of patients; renal impairment (RI), defined as CrCl <50 ml/min: 28% of patients (range of CrCl: 13-49 ml/min). Thirty-six patients started with lenalidomide dose of 25mg/day and 10 patients with dose adjusted to renal function (10mg/day: 7 patients, 15mg every other day: 2 patients, 15 threetimes a week after dialysis: 1 patient). Response according to IMWG criteria include: CR: 17%, vgPR:5%, PR: 38%, SD: 22%, PD: 18% (PR or better: 60%). At least PR was observed in 43% of thalidomide-refractory patients, in 76% of bortezomib-refractory patients and in 20% of patients with high LDH. At least PR was documented in 60% of patients with RI and in 58% without RI. Median time to progression was 9 months and median overall survival was 16 months. Main toxicities include: neutropenia (grade 3/4): 26%; thrombocytopenia (grade 3/4): 11%; other toxicities (any grade): fatigue 50%, infections 28%, constipation 17%, diarrhea 15% and skin toxicity 11%. DVT prophylaxis with aspirin was administered to 39 patients (84%) and no patient developed DVT. Dose-reductions of lenalidomide were necessary in 46% of patients. There were no statistical differences in the incidence of adverse events in patients with normal or abnormal renal function. More specifically grade 3/4 thrombocytopenia and neutropenia occurred in 10% versus 11% (p=0.92) and 31% versus 10% (p=0.190) of patients with normal and abnormal renal function, respectively. The effect of treatment on RI reversal was also evaluated: 2 patients achieved complete renal response (i.e. baseline CrCl <50 ml/min improving to ≥60 ml/min) and 2 patients achieved minor renal response (baseline CrCl <15 ml/min improving to 15-29 ml/min or baseline CrCl 15-29 ml/min improving to 30-59 ml/min).Thus, in 4 of 10 patients with RI, treatment with RD resulted in improvement of renal function. We conclude that RD is an active treatment in patients with relapsed/refractory MM, even in patients with more heavily pretreated disease that those in the original report (Dimopoulos et al, N Engl J Med 2007;357:2123). RD is active in thalidomide and bortezomib refractory patients. With dosing of lenalidomide according to renal function, RD can be administered to patients with RI (who may not have other treatment options) without excessive toxicity. Furthermore, RD may improve the renal function in a subset of patients with RI. Disclosures: Dimopoulos: CELGENE: Honoraria.

Three Drug Combinations Based on Bortezomib and Dexamethasone (VD) Backbone Improve Renal Function More Efficiently Than VD in Myeloma Patients with Severe Renal Impairment

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4769-4769 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Maria Roussou ◽  
Evangelos Terpos ◽  
Erasmia Psimenou ◽  
Maria Gavriatopoulou ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Impairment ◽  
Median Time ◽  
Light Chain ◽  
Early Death ◽  
Drug Combinations ◽  
Renal Recovery ◽  
Newly Diagnosed ◽  
Renal Response ◽  
Significant Difference

Abstract Renal impairment (RI) is a frequent complication of multiple myeloma (MM) and is associated with significant morbidity and risk of early death. Patients with severe RI (eGFR <30 ml/min/1.73 m2) have worse outcome and are frequently excluded from clinical trials. Two or three drug combinations based on the bortezomib and dexamethasone (VD) backbone have been proposed by the IWMG as the treatment of choice for patients who present with RI. In order to evaluate if two or three drug combinations were more efficient in patients who present with severe RI, we studied 56 (28M/28F) consecutive, unselected, newly diagnosed MM patients with severe RI who were treated in our center (University of Athens, Greece). Assessment of the degree of RI was made with the MDRD formula. Severe RI was defined as an eGFR of <30 ml/min/1.73 m2. Renal complete response (CRrenal) was defined as a sustained increase of baseline eGFR to >60 ml/min/1.73 m2, renal partial response (PRrenal) as an increase of eGFR from <15 to 30-50 ml/min/1.73 m2 and renal minor response (MRrenal) as a sustained improvement of baseline eGFR of <15 ml/min/1.73 m2 to 15-29 ml/min/1.73 m2 or if baseline eGFR was 15-29 ml/min/1.73 m2, improvement to 30-59 ml/min/1.73 m2. The median age of patients was 65 years (range: 37-88 years) and 21% of them were >75 years of age. The median eGFR was 11.2 ml/min/1.73 m2 (range: 3.4- 29.2 ml/min/1.73 m2); 64% had eGFR <15 ml/min/1.73 m2, including 16 (28.5%) patients who received dialysis with regular filters. Median level of proteinuria was 1.8 g/24h (range 0.2-12 g/24h) and involved free light chain (FLC) was 4250 mg/l (range 4.4-35,200 mg/l). All patients received VD-based regimens: 23 (41%) received VCD, 18 (32%) received VD, 8 (14%) received VTD, 5 (9%) received PAD, and 2 (4%) patients received VMP. An improvement of renal function (at least MRrenal) was recorded in 39 patients (70%) within a median time of 21 days (range 4-152 days). CRrenal was documented in 43% of patients and PRrenal in 9% (major renal response rate of 52%). Seven of 16 (44%) patients who required dialysis became dialysis independent. The median time to major renal response was 28 days (range 7-152 days). Patients with eGFR ≥15 ml/min/1.73 m2 (p=0.06) and age <65 years (p=0.036) had more rapid renal recovery (≥PRrenal). The type of light chain, presence of hypercalcemia (≥11 mg/dl) and elevated serum LDH (≥250 U/L) were not predictive of the probability of renal response. Using ROC analysis, we identified serum FLCs >12,500 mg/L as a cut-off associated with major renal response: only 16% of patients with FLCs >12,500 mg/L achieved a major renal response vs 59% of the others (p=0.053). Three-drug combinations (VTD, VCD, PAD, VMP) vs VD alone were associated with higher probability of major renal responses (65% vs 26%; p=0.006). Myeloma response to treatment by IMWG criteria was predictive of major renal response (p=0.05) in the univariate analysis. In multivariate analysis, adjusted for age >65 years and need for dialysis, the use of three-drug combinations was independently associated with a higher probability of major renal response (OR: 3.91, 95% CI 1.014-15, p=0.048). There was also a trend towards a shorter time until a major renal response for patients treated with three vs two drugs (35 vs >90 days, p=0.14). There was no significant difference in the probability of major renal response or time to renal response for those who received VTD vs VCD, PAD or VMP, even after adjusting for need of dialysis and age. Among patients who required dialysis, 9 (56%) received a three drug combination (5 VTD, 3 VCD and one PAD); among patients who became independent of dialysis 3 received VTD, 1 PAD and 3 VD. An early death (within <2 months from treatment initiation) occurred in 6 (11%) patients (5 had received VD and only one VTD). The median survival for all patients was 53 months, similar for patients who achieved a major renal response vs those who did not (p=0.413). Toxicities were similar to those seen in myeloma patients without renal failure who were treated with bortezomib-based regimens. In conclusion, our data indicate that bortezomib–based regimens can improve renal function in the majority of patients with severe RI. Three drug combinations based on VD are associated with a higher probability of major renal response and with a shorter time to renal recovery and should be offered to all newly diagnosed patients with severe RI. The FLC level could be used as a predictive factor for renal response. Disclosures No relevant conflicts of interest to declare.

Phase 2 Study of Carfilzomib, Thalidomide, and Low-Dose Dexamethasone As Induction/Consolidation in Newly Diagnosed, Transplant Eligible Patients with Multiple Myeloma, the Carthadex Trial

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1141-1141 ◽  
Author(s):  
Ruth Wester ◽  
Bronno van der Holt ◽  
Emelie Asselbergs ◽  
Mark van Duin ◽  
Sonja Zweegman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Risk ◽  
Induction Therapy ◽  
Research Funding ◽  
Fixed Dose ◽  
Phase 2 ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
Standard Risk

Abstract Introduction A phase 2 dose escalation trial of Carfilzomib in combination with Thalidomide and Dexamethasone (KTd) for induction and consolidation in newly diagnosed, transplant-eligible patients with multiple myeloma (MM). We report the results of 4 dose levels. Methods In this multicenter, open-label, phase 2 trial, transplant-eligible patients aged between 18 and 65 years with previously untreated symptomatic MM were included. Patients were treated with 4 cycles of escalating dose of Carfilzomib + fixed-dose thalidomide and dexamethasone (KTd) for induction therapy. The dose of Carfilzomib was 20 mg/m2 i.v. on days 1, 2 followed by 27 mg/m2 on days 8, 9, 15, 16 of cycle 1 and on days 1, 2, 8, 9, 15 and 16 of cycles 2 to 4. Thalidomide dose was 200 mg orally on days 1 through 28 and Dexamethasone 40 mg orally on days 1, 8, 15 and 22. Carfilzomib was escalated to 20/36 mg/m2 in cohort 2, to 20/45 mg/m2 in cohort 3 and to 20/56 mg/m2 in cohort 4. Induction was followed by stem cell harvest after Cyclophosphamide priming (2 to 4 mg/m2) and G-CSF. Hereafter patients received high-dose Melphalan (HDM, 200mg/m2) and autologous stem cell transplantation followed by consolidation treatment with 4 cycles of KTd in the same schedule except a lower dose of Thalidomide (50mg). The primary endpoint was response after induction therapy and overall, specifically complete response (CR) and very good partial response (VGPR). Secondary endpoints were safety, progression-free survival (PFS) and overall survival (OS). Results All 111 patients with a median follow-up of 55, 42, 35 and 28 months, in cohorts 1 to 4, respectively were included in the analysis. Median age was 58 years. ISS stages I/II/III were 41%/34%/23%, respectively, R-ISS stages I/II/III/unknown were 23%/59%/9%/9%, respectively. Of 111 patients, 9 patients stopped treatment during/after induction, 8 patients after cyclophosphamide priming or HDM and 9 patients during consolidation because of toxicity (n=9), non-eligibility for further treatment (n=6), progression (n=5), refusal (n=2) or other reasons (n=4). Overall response rate for all cohorts was 95%. Response after induction was CR/sCR in 18% of patients, ≥ VGPR in 66% of patients, ≥ PR in 94% of patients. After HDM the CR/sCR rate increased to 31% and after consolidation to 64%. Responses between cohorts were in general comparable. See Table 1. Response based on risk status by ISS/FISH in either cohort and accumulated did not show a difference in CR/sCR rate after consolidation between standard-risk (67%) and high risk defined as t(4;14) and/or del17p and/or add1q and/or ISS3 (60%). OS at 30 months was comparable between standard risk and high risk, 91% versus 90%. PFS at 30 months for standard risk and high risk was 79% and 62%, logrank p=0.02 (HR=2.3, 95% CI=1.1-4.5). PFS at 30 months per cohort was 70% (95% CI, 55% to 81%), 70% (95% CI, 45% to 85%), 80% (95% CI, 56% to 92%) and 62% (95% CI, 32% to 82%) in cohorts 1,2, 3 and 4, respectively, and 71% (95% CI, 61% to 79%) in all patients. OS at 30 months per cohort was 90% (95% CI, 77% to 96%), 90% (95% CI, 66% to 97%), 95% (95% CI, 71% to 99%) and 88% (95% CI, 58% to 97%) respectively, and 91% (95% CI, 83% to 95%) in all patients. Gene expression profiling using the Affymetrix U133 Plus 2.0 GeneChips was performed on purified tumor cells for 49 patients. Using the prognostic classifier EMC92 a high-risk group of patients (16%) was identified versus standard risk (in terms of OS: logrank p=0.06 (HR=3.7, 95% CI=0.8-16.8), and in terms of PFS: logrank p=0.14 (HR=2.1, 95% CI=0.8-6.0)). Safety analysis for all 111 patients showed non-hematological grade 3 and 4 toxicity, mainly respiratory disorders (in 15%), GI disorders (13%) and skin lesions (10%). Toxicity between cohorts did not show a significant difference. Cardiac adverse events were limited and included heart failure (n=2 at 27 mg/m2), hypertension (n=2) and chest pain (n=1 at 45mg/m2). Conclusion Carfilzomib, thalidomide, dexamethasone (KTd) is an effective regimen, with increasing CR percentages following KTd consolidation. With escalated doses of Carfilzomib responses and toxicity were comparable to standard dose of 27 mg/m2. Disclosures Zweegman: Takeda: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Kersten:Celgene: Research Funding; Amgen: Honoraria. Minnema:Celgene: Consultancy; BMS: Consultancy; Amgen: Consultancy; Jansen Cilag: Consultancy. Palumbo:Janssen Cilag: Honoraria; Takeda: Employment, Honoraria. Lokhorst:Genmab: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Broijl:Celgene: Honoraria; Amgen: Honoraria; Janssen: Honoraria. Sonneveld:Karyopharm: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Celgene: Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding.

Patients with Newly Diagnosed Multiple Myeloma and a Gain of the Long Arms of Chromosome 1 Have Inferior Outcomes, Including Early Onset Extramedullary Disease, Despite the Use of Novel Triplet Regimens

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4996-4996
Author(s):  
Noa Biran ◽  
Vesna Najfeld ◽  
Emily Bagiella ◽  
Sundar Jagannath ◽  
Ajai Chari
Keyword(s):  
Spinal Cord ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
High Risk ◽  
Overall Response Rate ◽  
Response Rate ◽  
Chromosome 1 ◽  
Newly Diagnosed ◽  
Inclusion Criteria ◽  
Novel Agent

Abstract Abstract 4996 BACKGROUND: In patients with newly diagnosed multiple myeloma (MM), a gain of the long arms of chromosome 1 is found in approximately 20% of patients by cytogenetics and 40% by FISH. A few studies have not found these abnormalities to be predictive of inferior progression free survival (PFS) and overall survival (OS) on multivariate analysis. The many studies that have were prior to the use of novel therapies in induction. Currently, testing for a gain or amplification of 1q21 locus is not included in the high risk genetic abnormalities by the International Myeloma Working Group (IMWG). Recently, two groups have reported inferior outcomes with bortezomib based induction regimens followed by high dose melphalan consolidation and maintenance therapy. The gain of 1q21 was either detected by cytogenetics or gene expression profiling (GEP70) at the University of Arkansas (Waheed et al, Cancer 2011) or by FISH in CD138 selected cells by the HOVON group (Neben et al, JCO 2012). However, the outcomes of these patients when treated with a bortezomib, lenalidomide, and dexamethasone induction regimen, which is associated with an overall response rate (ORR) of 100% and VGPR or better rate of 74% is unknown (Richardson et al. Blood 2010). Here, we describe the poor outcomes of patients with newly diagnosed MM with gain of 1q21 by FISH in unselected bone marrow aspirates despite novel agent triplet therapy. METHODS: The inclusion criteria for this IRB approved retrospective study were patients with symptomatic MM starting in June of 2008 who had a gain of 1q21 by FISH in 200 bone marrow interphase cells at the time of diagnosis. Patients with 1q amplification had at least 3 or more copies. PFS and OS were calculated by Kaplan-Meier analyses. RESULTS: 23 patients met the inclusion criteria. The median age was 59. 7 (range 46–71) and twenty patients (87%) were DS III at diagnosis, 13/23(57%) were ISS Stage 3. 6/23 (26%) had hypercalcemia, 8/23 (35%) had renal insufficiency, and 19/23 (83%) had anemia. Lytic lesions were present in 17/23 (74%) of patients at diagnosis. Of note, while 4 patients had deletion 13 by cytogenetics only 2 patients had other high risk findings, one with t(4;14) and another with deletion 17. All patients were treated with novel agent induction therapy. 19/23 (83%) were treated with triplet regimens (bortezomib, dexamethasone, and either lenalidomide or cyclophosphamide i. e. VRD or VCD). Disappointingly, primary induction failure, defined by PD or SD after 3–4 cycles, was observed in 30% of all patients. Of the 17 patients who received upfront triplet VRD or VCD therapy (with or without HDM plus SCR) the overall response rate (ORR) was only 77% (13/17), and 47% (8/17) achieved VGPR or better. More specifically, 3/17 (18%) had CR, 5/17 (29%) had VGPR, 5/17 (29%) had PR, 1/17 (6%) had SD and 1/19 (6%) had PD. Of the 4 patients who received novel doublet therapy (VD or RD) upfront, only 1 had a VGPR, one had SD and 2 had PD. The responses noted were not very durable, with a median PFS of 14 months. Although 3 patients have died (after 11–13 months from diagnosis), the median OS has not been reached with a median follow up of 13 months. Plasmacytomas of the bone with soft tissue expansion were present in 48% of the patients and 3 of 23 (13%) had spinal cord compression. Extra-osseous MM within 3 months of diagnosis was observed in 5/23 (22%) patients and 4/5 did not have any other high risk cytogenetics. Three patients (13%) had CNS MM at median of 5. 3 months after diagnosis. One patient had concomitant parenchymal brain lesions, myleomatous meningitis, and intra spinal cord disease. CONCLUSIONS: Even in the era of novel agent induction therapies, in our series of newly diagnosed 23 patients with a gain of 1q21, the failure rate of induction was 30% with a median PFS of 14 months. Moreover, these patients had a particularly aggressive clinical course with both medullary and extramedullary plasmacytomas, suggesting that PET-CTs, rather than just skeletal surveys should be considered for initial staging and monitoring. Also, given an unusually high incidence (13%) of early onset CNS disease, prompt CSF evaluation and brain MRI should be performed on patients with neurologic symptoms or signs. We recommend that gain or amplification of q21 identified either by FISH (even without CD138 selection – as demonstrated here) or GEP be prospectively studied in patients with newly diagnosed MM with consideration of novel therapeutic approaches. Disclosures: No relevant conflicts of interest to declare.

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