Multiple myeloma is one of the most common plasma cell neoplasms and mainly involves bone and bone marrow. It is not an uncommon disease in Korea. Previous studies in Korea included only small numbers of cases. In 1972 an initial statistical analysis of 28 cases was presented at the Korean Hematology Meeting¹⁾. A second report was made at the 4th International Hematology Meeting of Asia and Pacific Area²⁾. Additional studies concentrating on the M-protein were reported at the Korean Hematology Meeting in 1983³⁾. As of this writing, there has been no Korean report on the results of chemotherapy.

We, therefore, analyzed the clinical features and chemotherapeutic results of 61 patients with multiple myeloma who were diagnosed between January 1976 and June 1984 at Seoul National University Hospital.

Between January 1976 and June 1984, 61 consecutive patients were diagnosed as having multiple myeloma at Seoul National University Hospital. The diagnosis was established according to the criteria of the Southwest Oncology Group (SWOG)⁴⁾. The patients were clincally staged using the system developed by Durie and Salmon⁵⁾.

Twenty one patients were treated with melphalan and prednisone (MP, Table 1), and 25 patients with the M2 protocol (Table 2)⁶⁾. An objective response was defined as a reduction of 50% or more in serum M-protein concentration or in urine 24 hour light chain excretion⁷⁾. This protein response must be accompanied by normal serum calcium, serum albumin above 3 g/dl, and no progression of skeletal disease. Determination of treatment effect was limited to patients who had received at least 2 cycles of chemotherapy, and whose M-protein levels had been continuously monitored. Remission duration was defined as the period from the day when the M-protein concentration decreased to less than 50% of the pretreatment value to the day when it doubled from the lowest value obtained during the remission period. Survival curves were calculated from the start of the therapy using the Kaplan-Meier product limit method, and the log-rank test was used for the comparison of survival curves.

The annual incidence of multiple myeloma in the U.S.A. is 3 per 100,000 population, with a peak occurrence at ages 50 to 70 year⁸⁾. This disease rarely occurrs before 40 years of age, and is slightly more common in males than in females. The incidence in Korea is unknown, but it comprises about 0.3% of all malignancies in Korea⁹⁾. In this study, the peak incidence was at ages 50 to 59 years with a median of 54 years, and only 6 patients (10%) were younger than 40 years of age. The male to female ratio was 2.8 : 1.

Patients with myeloma have variable clinical manifestations. Bone pain is present in 68% of patients at diagnosis, anemia in 62%, and renal problems in 50%¹⁰⁾. Renal problems include proteinuria, tubular dysfunction, urinary tract infection, acute renal failure and chronic renal failure. Infection is frequent due to an abnormal immune system. The overall incidence is 1.46 infectious episodes per patient-year, and nearly 70% of patients with myeloma die as a result of infection¹¹⁾. The two months immediately following the start of initial chemotherapy was the most hazardous period. In this study, the most common clinical problems at initial presentation were bone pain (52%) and anemia (20%). Other problems include acute or chronic renal failure (11%), and infection (10%). Renal failure and infection were the most common causes of death.

Kyle et al. reported the relative distribution of immunoglobulin classes by serum and/or urine immunoelectrophoresis¹⁰⁾. It was IgG 59%, IgA 23%, IgD 1%, and light chain only 17%. In this study, it was IgG 50%, IgA 28%, IgD 8%, and light chain only 14%.

There are many prognostic factors influencing patient survival, among which serum creatinine level is considered the most important. Other prognostic factors include performance status, hemoglobin level, serum albumin and calcium level, degree of osteolytic lesion, and amount of M-protein. The clinical staging system was developed on these parameters⁵⁾. Santoro et al. reported that the median survival from diagnosis was 48 months for stage I, 41 months for stage II and 23 months for stage III¹²⁾. The median survival of patients with normal renal function was 35 months compared to 7 months for those with renal impairment. Response to chemotherapy is another important prognostic factor on patient survival^12,13). Patients who obtained objective responses survived much longer than those who did not. In this study, age, calcium level, creatinine level, performance status, and response to chemotherapy were found to be important prognostic factors. The median survival of patients with myeloma has been reported as 2 to 3 years⁸⁾. In this study the median survival of patients was 13 months. This poor result might be explained by the fact that the majority of patients in this study were in advanced stages at the initial presentation.

Treatment of multiple myeloma is composed of general supportive care and chemotherapy. Supportive care aims to preserve ambulation and mobility, control pain and avoid dehydration. Management of complications, i.e., control of hypercalcemia, skeletal destruction, infection and renal dysfunction is also an important aspect of supportive measures. However, definitive treatment of myeloma calls for chemotherapy. Current drugs shown to be effective as a single agent include alkylating agents (melphalan, cyclophosphamide, chlorambucil), nitrosoureas, procarbazine, and doxorubicin, each of which has a remission rate of about 20–50%^14–16). To improve the remission rate and to prolong the survival time many combination chemotherpay regimens were investigated. One of the most commonly employed regimens is a combination of melphalan and prednisone (MP), which showed a remission rate of 48% and remission duration of 24 months¹³⁾. The best reported results of combination chemotherapy are those based upon the M2 protocol developed by investigators at Memorial Sloan Kettering Cancer Center⁶⁾. This regimen combines melphalan, prednisone, cyclophosphamide, vincristine, and BCNU. A remission rate of 78–87% and median survival of 38–50 months were reported^6,17). The Eastern Cooperative Oncology Group compared this M2 protocol with MP therapy in a randomized study. Objective responses were seen in 74% of the patients receiving the M2 regimen, and in 53% of those receiving the MP regimen. But the median survival did not differ at 33 and 29 months, respectively¹⁸⁾. In our study, the MP regimen produced a 29% remission rate, and the M2 protocol 40%. This lower remission rate could be explained by the large numbers of patients in advanced disease in our stydy. When patients fail to respond to initial therapy or relapse after responding to first line drugs, second-line treatment may be tried. A combination chemotherapy with BCNU and doxorubicin was shown to have a response rate of 54% in relapsed patients¹⁹⁾. We treated 5 patients, 4 initial nonresponders and 1 relapsed patient, with BCNU and doxorubicin, but none of them responded. We think that more systematic and continous studies are required on this subject in Korea.