Clinical characteristics of patients (n=32)

Lab investigations

Sixteen patients (50%) had anemia according to the criteria satisfying myeloma-related tissue or organ impairment (Hb <10 href="https://www.thieme-connect.com/products/ejournals/html/10.4103/ijmpo.ijmpo_57_17#TB_2" xss="removed"> [Table 2]. All patients had bone marrow plasmacytosis more than 10% on marrow examination. The percentage of plasma cells> 70% was seen in 2 (6.3%) cases and between 50% and 70% in 3 (9.4%) and between 10% and 30% in 19 (59.4%) cases of study population. The mean bone marrow plasma cell percentage before therapy was found to be 31.26.97%.

Laboratory findings of the patients (n=32)

Treatment and outcome

Thirteen (40.6%) of 32 received cyclophosphamide, dexamethasone, and thalidomide regimen. Three (9.4%) patients received bortezomib, dexamethasone, and thalidomide regimen. Two (6.3%) of them received bortezomib, cyclophosphamide, and thalidomide regimen. Five (15.6%) cases received dexamethasone and thalidomide regimen. Of 32 patients, one patient expired during the treatment. The follow-up assessment showed that 20 (64%) of 32 patients had partial response to treatment and 7 (23%) had complete response. Four (13%) of them had stable disease not responding to treatment. All the patients who achieved either partial or complete response following treatment had a significant reduction in bone pain. It was noticed that one patient during the treatment complained of significant loss of appetite and weight with bleeding per rectum and melena. Further evaluation revealed moderately differentiating adenocarcinoma of stomach. Among the 13 (40.6%) patients who received cyclophosphamide, dexamethasone, and thalidomide regime, 4 (13%) had stable disease not responding to treatment. All the patients who received bortezomib therapy showed either partial or complete response and none of them had stable or progressive disease.

The mean bone marrow plasma cell percentage after therapy was 13.29% compared to 31.26 fore therapy. The comparison of means showed a significant difference between the mean plasma cell percentage before and after the treatment (t = 4.138 [degree of freedom = 30] and P = 0.0001).

Discussion

A high male:female ratio in our study was similar to the United Kingdom cancer research statistics in 2013 (57% males and 43% in women), giving a male:female ratio of 1.3:1.[9] Seventh decade was found to be the most common age group in our study population and the mean age was 64 10.77 years. Sixth decade was the most common age group at presentation in Asian myeloma network study [10] and an Indian study by Kaur et al.[11] The most common symptoms were fatigue 32 (100%) and bone pain 31 (96.9%). Kyle et al.,[12] from mayo clinic in Rochester, reported bone pain as the predominant symptom (68%). Majority of our study population (29, 90.6%) had spine tenderness on examination. Most common clinical presentation (56%) was bone related such as bony swelling, bone pain, low backache, and pathological fractures in an Indian study.[13]

Sixteen (50%) patients had anemia according to the criteria satisfying myeloma-related tissue or organ impairment (Hb <10 href="https://www.thieme-connect.com/products/ejournals/html/10.4103/ijmpo.ijmpo_57_17#JR_11" xss=removed>11]

Hypercalcemia, even though considered as one among the important diagnostic criteria (CRAB symptoms), was seen only in six (18.8%) patients. Kyle?et al.[12] also reported hypercalcemia only among 13% of the 1027 patients.[12] Diagnosis of MM was made in those with normal calcium 21 (66%) and below normal levels 5 (16%). Low calcium levels might be due to renal impairment. However, 2 (6%) patients had low calcium levels without renal impairment. Hypocalcemia in MM secondary to Vitamin D deficiency was reported previously.[14] Factors including vitamin D deficiency may be contributing to hypocalcemia other than renal failure in myeloma patients.

Renal impairment was seen only in 7 (21%) patients. Studies by Kyle?et al.[12] and Kaur?et al.[11] showed a significant renal impairment (55% and 86.4%, respectively). The underlying cause for renal failure in MM can be hypercalcemia or myeloma kidney itself. Low serum albumin level was found in majority of the patients 20 (62.5%). Combination of albumin and serum ?2 microglobulin forms the basis for a three stage international staging system that predicts survival.[3] Serum albumin level was found to be a significant prognostic factor for assessing disease severity in symptomatic MM in a previous study.[15]

Thirty (94%) patients had a thick M-band in serum protein electrophoresis and the most common site was the gamma globulin region. In the study by Kyle?et al.,[12] 82% had M-band.

Thirteen (40.6%) cases received cyclophosphamide, dexamethasone, and thalidomide regimen. Three (9.4%) of them received bortezomib, dexamethasone, and thalidomide regimen. Although bortezomib has showed good results in various studies,[16],[17] its use is limited in our center because of the financial burden and cost factor. The socioeconomic status of the patients being treated from our center, as already mentioned, majority comes under Class IV according to BG Prasad's socioeconomic classification, and hence, cost affordability is one of the important issues with bortezomib even though now being a good choice in frontline therapy of MM. Bortezomib can be part of any treatment regimen and lack of renal excretion helps in its use in patients presenting with renal failure. Use of subcutaneous administration and once-weekly schedule has decreased the neurological toxicity and allows for its extended use. Various studies also suggests its better efficacy and outcome and can be presently used as a first-line agent.[18] Some studies also shows significant improvement in survival and better efficacy when used for induction and maintenance treatment as well as before and after autologous stem cell transplantation.[19] After its approval by the US and European regulatory authorities for the treatment of MM, there have been a large number of studies confirming better results with the drug.

Due to limitations in our study because of financial constraints of the study group, we were unable to do serum-free light chain assay as already mentioned previously which forms part of uniform response criteria for reassessment after treatment. Hence, it was not possible to strictly adhere with the uniform response criteria suggested by international myeloma working group. However, we reassessed the study group after treatment based on the disappearance of M-band by serum protein electrophoresis and reduction of bone marrow plasma cell percentage. The follow-up assessment showed that majority (64%) showed partial response to treatment and 7 (23%) showed complete response. Four (13%) of them had stable disease not responding to treatment. The mean bone marrow plasma cell percentage after therapy was 13.29% compared to 31.26?fore therapy. A similar study showed that 10 (56%) patients had complete response and 8 (44%) had partial response.[13] The mean bone marrow plasma cell percentage at the end of therapy was 2% compared to 56?fore therapy in their study.[13]

The reassessment of clinical features showed that all the patients who achieved either partial or complete response following treatment had a significant reduction in bone pain. One patient during the treatment had significant loss of appetite and weight with bleeding per rectum and melena. Further evaluation revealed moderately differentiating adenocarcinoma of stomach. A similar rare presentation of coexistent MM with gastric carcinoma was reported in a 77-year-old male patient.[20]

Among the 13 (40.6%) cases who received cyclophosphamide, dexamethasone, and thalidomide regimen, 4 (13%) had stable disease not responding to treatment. All the 6 (19%) patients treated with bortezomib showed either partial or complete response showing the efficacy of bortezomib in our study population. The response achieved with bortezomib was much better than with cyclophosphamide, dexamethasone, and thalidomide regimen in our study group, as suggested by 4 (13%) of the patients having a stable or progressive disease with cyclophosphamide-based regimen and none had the same with bortezomib.

Conclusions

To conclude, the patients with MM in the present study had a male preponderance with a male to female ratio of 1.3:1. Seventh decade was found to be the most common age group at presentation. Most common symptoms noticed were fatigue and bone pain and majority had spine tenderness on examination. Hypercalcemia, even though considered as one among the important diagnostic criteria was seen in few patients. The presentation of MM is nonspecific and patient can come with varied presentations at onset. The quality of life and survival in MM patients can be improved significantly if there is access to newer therapies.

Conflict of Interest

There are no conflicts of interest.

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