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  Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 54  |  Issue : 1  |  Page : 340-342
 

Multiple myeloma: Experience of an institute in limited resource setting


Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India

Date of Web Publication1-Dec-2017

Correspondence Address:
Ankit Agarwal
Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijc.IJC_87_17

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 » Abstract 

INTRODUCTION: Multiple myeloma (MM) is a plasma cell dyscrasias and an incurable clonal B-cell malignancy, with an annual incidence of 1% of all malignancies. The mainstay of treatment of myeloma is induction treatment followed by consolidation with autologous stem cell transplant (ASCT). However, still in a developing country like India where affordability is a major hurdle for health care, a number of MM patients are not able to undergo ASCT. AIM: To study the epidemiological features and outcome of MM patients treated in a limited resource setting. MATERIALS AND METHODS: We conducted a retrospective study at our institute to identify patients diagnosed as MM from 2005 to 2016. We studied the epidemiological profile and the outcome of the treatment in terms of response rates and overall survival. STATISTICAL ANALYSIS: Survival analysis was performed using Kaplan–Meier curve. RESULTS: Median age at diagnosis is 54 years (range: 39–85 years). IgG myeloma was the most common type seen in 72% of patients. The International Staging System (ISS) was ISS I (31%), ISS II (30%), and ISS III (39%). The median duration of treatment for thalidomide + dexamethasone (TD) and bortezomib + TD (VTD) was 9 and 7 months, respectively. Median survival for the TD versus VTD regimen (in a nontransplant setting) for the ISS I, ISS II, and ISS III groups was 49 and 55 months (P = 0.056), 42 and 48 months (P < 0.05), 21 and 27 months (P < 0.05), respectively. CONCLUSION: Proteasome inhibitors significantly improved the median survival for patients with MM (ISS II and ISS III) treated in a limited resource setting.


Keywords: Institute experience, limited resource setting, multiple myeloma


How to cite this article:
Jacob LA, Suresh Babu M C, Lakshmaiah K C, Babu K G, Lokanatha D, Rajeev L K, Lokesh K N, Rudresha A H, Agarwal A, Garg S. Multiple myeloma: Experience of an institute in limited resource setting. Indian J Cancer 2017;54:340-2

How to cite this URL:
Jacob LA, Suresh Babu M C, Lakshmaiah K C, Babu K G, Lokanatha D, Rajeev L K, Lokesh K N, Rudresha A H, Agarwal A, Garg S. Multiple myeloma: Experience of an institute in limited resource setting. Indian J Cancer [serial online] 2017 [cited 2020 Jul 4];54:340-2. Available from: http://www.indianjcancer.com/text.asp?2017/54/1/340/219603



 » Introduction Top


Multiple myeloma (MM) (from Greek “myelo” - bone marrow) is a plasma cell dyscrasias and an incurable clonal B-cell malignancy, with an annual incidence of 1% of all malignancies and 10% of all hematological malignancies. It is characterized by the presence of a serum monoclonal protein, renal failure, osteolytic bone lesions, hypercalcemia, and anemia. There are approximately 19,000 new cases/year in the United States of America and an Indian incidence of 6000 new cases/year.[1] Plasma cell dyscrasias can be broadly subdivided into the following heads:

  • Monoclonal gammopathy of unknown significance (MGUS)
  • Plasmacytoma – Solitary mass of neoplastic monoclonal plasma cells in either bone or soft tissue (extramedullary)
  • Asymptomatic myeloma
  • Symptomatic myeloma.


MM evolves from a premalignant condition clinically recognized as MGUS.[2] Until 2000, the mainstay of therapy for MM was the use of alkylators and corticosteroids,[3] and in selected patients, high-dose chemotherapy with autologous stem cell transplant (ASCT).[4],[5] Subsequently, thalidomide, bortezomib, and lenalidomide emerged as effective agents and greatly improved the clinical outcome. More recently, carfilzomib, pomalidomide, panobinostat, daratumumab, ixazomib, and elotuzumab have been approved in the United States for the treatment of MM, substantially expanding the number of treatment regimens available for patients in all stages of the disease. However, still in a developing country like India where affordability is a major hurdle for health care, a number of MM patients are not able to undergo ASCT even after achieving complete response (CR)/very good partial response postinduction. Our data here provide details about the outcome of MM patients treated in a limited resource setting.

Aim

To study the epidemiological features and determine the outcome of MM patients treated in a limited resource setting.


 » Materials and Methods Top


We conducted a retrospective study at our institute to identify all the patients diagnosed as MM from 2005 to 2016. The diagnosis of MM was based on the International Myeloma Working Group criteria 2003 (updated in 2009 and 2014) as shown in [Table 1].[6] The pretreatment evaluation included the presenting symptoms, age, sex, skeletal survey, serum protein electrophoresis, serum β2 microglobulin, free light chain assay, bone marrow study results, complete blood count, biochemistry profile, and staging by the International Staging System (ISS) [Table 2].[7] We also studied the treatment given to the patients and the outcome of the treatment in terms of overall survival.
Table 1: Diagnosis of symptomatic multiple myeloma (International Myeloma Working Group criteria)[6]

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Table 2: International staging system (ISS)

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 » Results Top


A total of 448 patients were diagnosed with symptomatic MM over a period of 12 years. Out of 448 patients, complete pretreatment laboratory values were available for 389 patients. [Table 3] shows the epidemiological features of the patients. The median age at diagnosis was 54 years (range: 39–85 years), with a male:female ratio of 2.1:1. Totally 39 patients (10%) were younger than 45 years of age. The common presenting features were bony pains (71%) and anemia (72%). Around 2% of patients were diagnosed on the basis of the presence of extramedullary plasmacytoma and CRAB is hypercalcemia (>11mg/dl), renal failure (creatinine clearance <40ml/min), anemia (Hb<10mg/dl), one or more bone lytic lesions on CT/MRi or PET-CT. Rest of the 98% had bone marrow plasma cell of at least 10% along with CRAB features. Hypercalcemia (range: 12–15.6 mg/dl) was seen in 23%, renal failure (serum creatinine range: 2–7.8 mg/dl) was present in 27%, and motor neuropathy due to spinal nerve compression was seen in 5% of patients. The most common monoclonal gammopathy was IgG (72%), IgA (10%), and light chain disease was seen in 16% of patients as shown in [Figure 1]. Among the 389 patients, 58% received thalidomide + dexamethasone (TD), 24% received bortezomib + TD (VTD), 1.6% received single-agent dexamethasone, 2.8% of the patients received lenalidomide + dexamethasone, 6% underwent high-dose therapy/ASCT, and rest 7.6% received various other regimens (vincristine, adriamycin, dexamethasone; melphalan, prednisolone; cyclophosphamide, bortezomib, and dexamethasone) as listed in [Table 4].[7] All the patients received zoledronic acid (dose adjusted according to their creatinine clearance values). The median duration of treatment was 9 and 7 months for TD and VTD, respectively. Patients who received VTD had a superior response rate (overall response 87%, CR 29%) as compared to patients who received TD regimen (overall response rate 70%, CR 7%) as depicted in [Table 5]. Survival analysis comparing TD and VTD regimens (comprising 82% of the different regimens used) was done using Kaplan–Meier graph [Figure 2]. Median survival for TD and VTD was 40 and 48 months, respectively. The median overall survival (OS) for patients classified as ISS I was 55 months for VTD regimen and 49 months for TD regimen (P = 0.056). The median OS for patients classified as ISS II was 48 months for VTD regimen versus 42 months for TD regimen (P = 0.0007). The median OS for patients classified as ISS III was 27 months for VTD and 21 months for TD (P = 0.00198). Survival analysis for patients who received treatment other than VTD and TD was not done in view of very small number of patients.
Table 3: Patient characteristics (n=389)

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Figure 1: Percentage of patients with different monoclonal gammopathies

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Table 4: Treatment details

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Table 5: Treatment response

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Figure 2: Overall survival: thalidomide + dexamethasone versus bortezomib + thalidomide + dexamethasone - Kaplan–Meier curve (median overall survival: 40 vs. 48 months, P < 0.001)

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 » Discussion Top


MM is one of the plasma cell dyscrasias, characterized by bone marrow infiltration with clonal plasma cells, production of monoclonal immunoglobulin (paraprotein), and associated with end-organ damage including lytic lesions in the bones, renal impairment, hypercalcemia, and anemia. MM is a disease of the elderly population (median age: 66 years).[8] Our study shows that the median age at diagnosis is 54 years which is 10 years earlier as compared to the Western population. In addition, the number of patients diagnosed as ISS III was higher in our study (39%) as compared to the Western data (percentage of patients in ISS III was 18%) where the maximum number of patients were in ISS II.[8] Cytogenetics data are not available for patients, so revised ISS is not used for the classification of patients. The data on the number of patients presenting with bone pains, anemia, fatigue, renal failure, and hypercalcemia were comparable to the Western data. The number of patients with IgG type of myeloma was 72% in our study in comparison to 50% as per the data from Mayo Clinic.[8] The number of patients who received TD induction treatment was 58%. Proteasome inhibitor bortezomib was given to 24% of the patients (VTD regimen). The data in our study show that 30% of the patients progressed while on TD regimen as compared to 13% on VTD regimen. Due to the limited availability of resources, alkylating agents such as melphalan (in combination with prednisolone) and cyclophosphamide were the only options for patients with progressive disease. Our study also shows that the VTD regimen is significantly better as compared to TD regimen in terms of median survival for ISS II (median OS: 48 vs. 42 months) and ISS III (median OS: 27 vs. 21 months) group of patients. The difference in median survival for patients in the group ISS I was not significant (median OS: 42 vs. 38.5 months, P value was not significant probably due to small number of patients in the VTD arm). The median survival in our study for the VTD regimen versus TD regimen is 48 months and 40 months (P< 0.001), respectively. The survival for our patients is inferior as compared to the Western data where the 5-year survival posttransplant for ISS I, ISS II, and ISS III is 82%, 62%, and 40%, respectively.[9] This difference in survival is due to the routine use of ASCT, maintenance therapy, and routine access to second-line therapy for treating patients in the Western world.


 » Conclusion Top


Proteasome inhibitors significantly improve the median survival for patients with MM (ISS II and ISS III) treated in a limited resource setting.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 » References Top

1.
Raab MS, Podar K, Breitkreutz I, Richardson PG, Anderson KC. Multiple myeloma. Lancet 2009;374:324-39.  Back to cited text no. 1
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2.
Kyle RA, Therneau TM, Rajkumar SV, Offord JR, Larson DR, Plevak MF, et al. Along-term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med 2002;346:564-9.  Back to cited text no. 2
[PUBMED]    
3.
Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: An overview of 6,633 patients from 27 randomized trials. Myeloma Trialists' Collaborative Group. J Clin Oncol 1998;16:3832-42.  Back to cited text no. 3
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4.
Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, et al. Aprospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome. N Engl J Med 1996;335:91-7.  Back to cited text no. 4
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5.
Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 2003;348:1875-83.  Back to cited text no. 5
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6.
Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014;15:e538-48.  Back to cited text no. 6
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7.
Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Bladé J, et al. International staging system for multiple myeloma. J Clin Oncol 2005;23:3412-20.  Back to cited text no. 7
    
8.
Attal M, Lauwers-Cances V, Hulin C, Facon T, Caillot D, Escoffre M, et al. Autologous transplantation for multiple myeloma in the era of new drugs: A phase III study of the Intergroupe Francophone du Myelome (IFM/DFCI 2009 Trial). Blood 2015;126:391.  Back to cited text no. 8
    
9.
Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, et al. Revised international staging system for multiple myeloma: A report from International Myeloma Working Group. J Clin Oncol 2015;33:2863-9.  Back to cited text no. 9
[PUBMED]    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

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