Renal recovery following daratumumab, lenalidomide, and dexamethasone therapy in a patient with newly diagnosed dialysis-dependent multiple myeloma

8096 Background: The combination of lenalidomide and dexamethasone (Len-Dex) is a commonly used initial therapy for newly diagnosed multiple myeloma. While the short-term outcomes with respect to response and toxicity is well-known, long-term outcome with this combination as initial therapy is not well described. Methods: We studied 286 consecutive patients with newly diagnosed MM seen at our institution, who received initial therapy with Len-Dex, and who had complete follow up records. Data regarding the clinical course was obtained from medical records. Results: The median (range) age at diagnosis was 63 (28-92) yrs; 166 (58% were ≤ 65 yrs and175 (61%) were male. The median estimated follow-up was 3.9 yrs (95% CI, 3.4, 4.2) and 203 (71%) pts were alive at the time of last follow up. The median estimated duration on Len-Dex was 5.3 mos (95% CI, 4.6, 6.4). The best overall response (≥PR) was 72%, including 26% with VGPR or better and 14 (5%) not being evaluable for a response. At last follow up, 41 (14%) patients were continuing on therapy. There were 93 pts (32%) who stayed on therapy for 12 months or more. Among these patients, the ORR was 86%, including 45% with VGPR or better. The median overall survival (OS) for the entire cohort from diagnosis was 7.4 yrs (95% CI; 5.8, NR) and the estimated 5-yr survival was 67%. There were 16 (5.5%) pts who died within a year of diagnosis. The median time to first disease progression, irrespective of transplant status, was 30.2 mos (95% CI, 25, 42). Overall, 143 (50%) of the patients have gone to stem cell transplant. Censoring those patients who proceeded to SCT prior to relapse at the time of BMT, the median TTP was 25.5 mos (95% CI, 22, 29). The median OS was 7.4 yrs for those ≤65 yrs, compared with 6.2 yrs for the older patients (P=0.01). The 5-yr OS estimate for patients in ISS stage 1, 2 and 3 were 82, 65, and 44 months respectively. Conclusions: The current study provides long-term estimates of responses and survival in a series of patients treated initially with lenalidomide and dexamethasone. The median survival of nearly 8 years reflects the efficacy of the novel agents both at diagnosis and at relapse and confirms the survival improvements seen in MM in the last decade.

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Disparities in Renal Recovery Between African Americans Vs. Non African Americans Following Initial Treatment of Newly Diagnosed Multiple Myeloma: A Retrospective Chart Review

Blood ◽

10.1182/blood.v128.22.5610.5610 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5610-5610

Author(s):

Benjamin A Derman ◽

Sanjib Basu ◽

Agne Paner

Keyword(s):

Chronic Kidney Disease ◽

Multiple Myeloma ◽

Overall Survival ◽

African Americans ◽

Kidney Disease ◽

Initial Treatment ◽

Chart Review ◽

Retrospective Chart Review ◽

Renal Recovery ◽

Newly Diagnosed

Abstract Introduction: Renal insufficiency (RI) in newly diagnosed multiple myeloma (NDMM) represents a poor prognostic factor (Knudsen, Hjorth, and Hippe 2000). Recent clinical trials have demonstrated that patients treated with novel agents, particularly proteasome inhibitors, may experience renal recovery with improvement in overall survival (Dimopoulos et al. 2013; Gonsalves et al. 2015). The majority of patients in these trials were Caucasians, although multiple myeloma is twice as common in African Americans (AA) as it is in Caucasians. Moreover, AA have a 5 times higher rate of stage 4 chronic kidney disease (CKD) and end-stage-renal-disease (ESRD) in the United States compared to Caucasians. The cause for this disparity is thought to be multifactorial, including a higher incidence of comorbidities such as diabetes and hypertension among AAs (Williams and Pollak 2013; Grams et al. 2013). There is currently a dearth of evidence regarding renal recovery in AA receiving therapy for MM. The goal of this study is to compare renal recovery between AA and non AA patients following initial treatment for NDMM. Methods: We performed a retrospective chart review of patients with NDMM at Rush University Medical Center from January 1, 2005 to August 1, 2016. 690 charts were selected and reviewed; patients who were on hemodialysis for alternative reasons prior to diagnosis, had a GFR > 90, or for whom records were incomplete were excluded. 118 patients with NDMM and a GFR < 90 (corresponding to National Kidney Foundation's chronic kidney disease stage 2 or worse) at the time of diagnosis were identified. Continuous variables were compared between the two groups using the Mann-Whitney U test, and binary variables were compared using Fisher's exact test. Results: We compared 59 AA and 59 non AA patients with RI at the time of diagnosis of MM. Both groups were comparable by age, gender, ISS and high risk cytogenetics. The degree of RI at the time of diagnosis was similar: median GFR at diagnosis was 47.89 in the AA group and 51.95 in the non AA group (p=0.56). Hypertension was more common in the AA group (78% vs. 52.5%, p=0.0064), while other comorbidities were statistically comparable. The majority of patients were treated with a bortezomib-based regimen (86.4% for the AA group and 84.7% for the non AA group, p=1). MM response rates to induction therapy were similar: very good partial response (VGPR) or better was achieved in 39% of AA and 25.4% of non AA (p=0.17). 45.8% of AA patients underwent autologous stem cell transplant (ASCT) compared to 64.4% of non-AA (p=0.0637, see table 3). 80% of AA and 88% of non AA patients received bisphosphonates (see table 1). Although median GFR at the time of diagnosis of MM was similar between the AA and non AA groups (47.89 vs. 51.95, p=0.56), the median absolute change in estimated GFR after initial therapy was significantly higher in the AA group (+33.64) vs. the non-AA group (+21.07, p=0.00183). This difference remained whether the baseline GFR at diagnosis was <90 or <60 (see table 2). The median time to best renal response was 91 days in AA and 79 days in non-AA (p=0.383). Conclusions: This is the first study to analyze disparities in renal dysfunction and recovery between AA and non-AA patients with NDMM. We demonstrate that in our institution AA patients with NDMM treated in the era of novel agents have greater improvement in renal function in comparison to non AA patients. Given that renal recovery in NDMM impacts overall survival, this finding suggests that further studies should be done to explore differences in the epidemiology and disease biology that could account for the racial disparities in renal dysfunction and recovery. Disclosures No relevant conflicts of interest to declare.

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Long-term outcome with lenalidomide and dexamethasone therapy for newly diagnosed multiple myeloma

Leukemia ◽

10.1038/leu.2013.143 ◽

2013 ◽

Vol 27 (10) ◽

pp. 2062-2066 ◽

Cited By ~ 24

Author(s):

G Srivastava ◽

V Rana ◽

M Q Lacy ◽

F K Buadi ◽

S R Hayman ◽

...

Keyword(s):

Multiple Myeloma ◽

Newly Diagnosed ◽

Term Outcome ◽

Long Term Outcome ◽

Dexamethasone Therapy

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Fatal amebic colitis after high-dose dexamethasone therapy for newly diagnosed multiple myeloma

Annals of Hematology ◽

10.1007/s00277-010-0984-3 ◽

2010 ◽

Vol 90 (2) ◽

pp. 225-226 ◽

Cited By ~ 7

Author(s):

Chiharu I. Kobayashi ◽

Go Yamamoto ◽

Akimasa Hayashi ◽

Satoshi Ota ◽

Yoichi Imai ◽

...

Keyword(s):

Multiple Myeloma ◽

High Dose ◽

Newly Diagnosed ◽

Amebic Colitis ◽

High Dose Dexamethasone ◽

Dexamethasone Therapy

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RNA-seq of newly diagnosed patients in the PADIMAC study leads to a bortezomib/lenalidomide decision signature

Blood ◽

10.1182/blood-2018-05-849893 ◽

2018 ◽

Vol 132 (20) ◽

pp. 2154-2165 ◽

Cited By ~ 5

Author(s):

Michael A. Chapman ◽

Jonathan Sive ◽

John Ambrose ◽

Claire Roddie ◽

Nicholas Counsell ◽

...

Keyword(s):

Multiple Myeloma ◽

Nearest Neighbor ◽

Residual Disease ◽

Progression Free Survival ◽

Standard Of Care ◽

Gene Signature ◽

The United States ◽

Newly Diagnosed ◽

Data Set ◽

Dexamethasone Therapy

Abstract Improving outcomes in multiple myeloma will involve not only development of new therapies but also better use of existing treatments. We performed RNA sequencing on samples from newly diagnosed patients enrolled in the phase 2 PADIMAC (Bortezomib, Adriamycin, and Dexamethasone Therapy for Previously Untreated Patients with Multiple Myeloma: Impact of Minimal Residual Disease in Patients with Deferred ASCT) study. Using synthetic annealing and the large margin nearest neighbor algorithm, we developed and trained a 7-gene signature to predict treatment outcome. We tested the signature in independent cohorts treated with bortezomib- and lenalidomide-based therapies. The signature was capable of distinguishing which patients would respond better to which regimen. In the CoMMpass data set, patients who were treated correctly according to the signature had a better progression-free survival (median, 20.1 months vs not reached; hazard ratio [HR], 0.40; confidence interval [CI], 0.23-0.72; P = .0012) and overall survival (median, 30.7 months vs not reached; HR, 0.41; CI, 0.21-0.80; P = .0049) than those who were not. Indeed, the outcome for these correctly treated patients was noninferior to that for those treated with combined bortezomib, lenalidomide, and dexamethasone, arguably the standard of care in the United States but not widely available elsewhere. The small size of the signature will facilitate clinical translation, thus enabling more targeted drug regimens to be delivered in myeloma.

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A Study of Lenalidomide Based Chemotherapy in Multiple Myeloma in Indian Population: Special Appraisal of Thromboembolic Risk.

Blood ◽

10.1182/blood.v114.22.4206.4206 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4206-4206

Author(s):

Velu Nair ◽

Satyaranjan Das ◽

Sanjeevan Sharma ◽

V. K. Jha ◽

S. Bhattacharya ◽

...

Keyword(s):

Multiple Myeloma ◽

Venous Thromboembolism ◽

Conflicts Of Interest ◽

Treatment Regime ◽

Lower Limbs ◽

Newly Diagnosed ◽

Experienced Radiologist ◽

Highly Effective ◽

Dexamethasone Therapy ◽

D Dimer

Abstract Abstract 4206 Introduction Multiple myeloma is a plasma cell tumor which accounts for about 10% of hematological malignancies. In recent years some advances in the management of this malignancy have been achieved, especially the newer drugs like thalidomide, lenalidomide and bortezomib. Lenalidomde, a second generation immunomodulatory drug has been shown in various series to be a highly effective agent in management of newly diagnosed as well as relapsed cases of myeloma. The incidence of venous thromboembolism in patients of myeloma taking Lenalidomide – Dexamethasone therapy has been reported as high as 17 %. The risk of thromboembolism is to some extent determined by genetic predisposition of a population. There are no published reports from the Indian subcontinent addressing the incidence of venous thromboembolism in patients with newly diagnosed or relapsed multiple myeloma treated with Lenalidomide – Dexamethasone. Patients and Methods Forty one consecutive patients diagnosed at our centre with multiple myeloma either afresh (n=30) or relapsed on a previously different treatment regime (n=11), were studied between Oct2007 to Jul 2009. Diagnosis was based on serum electrophoresis and immunofixation, bone marrow plasmacytosis, and relevant tissue involvement. Patients were staged as per Durie Salmon system, and all our cases were found to be in stage 3 (3A = 34 cases, 3B = 7 cases). Detailed baseline clinical, haematological, and biochemical parameters were recorded. Colour Doppler flow imaging (CDFI) using a Philips 5000 imager of the lower limbs by an experienced radiologist was performed in all patients for DVT. D dimer using immunoturbidometric semi quantitative slide agglutination assay which measures fibrinogen equivalent units which is usually twice the actual D dimer value (<1.0 mcg/ml as normal cut off, 1.0 – 2.5 mcg/ml as indeterminate) was measured in all cases at diagnosis. All patients were started on therapy with Lenalidomide 25 mg a day for 21 consecutive days every month, with dose modification for renal insufficiency as per GFR. Dexamethasone 40 mg a day for first four days was given to all cases. Low dose aspirin 75 mg / d was used as thromboprophylaxis. Patients were followed up monthly with clinical, haematological and biochemical monitoring, specifically looking for any progression of myeloma parameters. Screening for occurrence of DVT was done using CDFI, D dimer, and thorough clinical examination at baseline and at one, three and six months interval from initiation of therapy. Results We report an overall response of 95% (nCR + CR : 30%) in newly diagnosed cases of multiple myeloma and 81.8% (nCR + CR : 36%) in patients with thalidomide failure / intolerant group. The primary toxic effect of lenalidomide was haematological and was manageable with dose adjustment of lenalidomide and supportive care. D dimer levels were found to be in the range of 0.5 to 2.4 mcg/ml (mean = 1.46 mcg/ml). On detailed follow up for upto six months there was no episode of venous thromboembolism recorded in any of the patients. All patients were asymptomatic for DVT and CDFI of lower limbs was normal at all points of examination in all patients of myeloma, newly diagnosed or relapsed. Conclusion Lenalidomide – Dexamethasone therapy is a highly effective regime for treatment of newly diagnosed and relapsed myeloma patients. In our cohort of both relapsed and fresh cases (n=41), on thromboprophylaxis with 75 mg asprin, not a single case of DVT was documented, proving its safety profile for venous thromboembolism. Larger trials would however be required to ascertain the exact risk of thromboembolism in patients of myeloma taking this treatment regime. Disclosures: No relevant conflicts of interest to declare.

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