Genetic and epigenetic events combined with environmental exposures may combine to initiate the oncogenic process leading to myeloma with or without immunoglobulin secretion. We expect to find significant differences between serum myeloma protein and Igs that highlight their unique and redundant roles in MM pathogenesis.
There are an estimated 18,900 new cases of multiple myeloma per year in the United States. This makes multiple myeloma the tenth most common cancer in the country. At the current rate of new diagnoses, it is expected that the number of cases of multiple myeloma will substantially increase in the next decade.
Treatment includes chemotherapy to induce and maintain remission, autotransplant to control the disease, and/or radiotherapy. Most patients are treated with these treatments before considering bone marrow transplant and/or stem cell transplant as they become available.
Signs of MM include bone and bone marrow lesions, which may be painful and associated with numbness (paresthesia) and decreased range of motion, weakness, loss of appetite, and, in severe cases, anemia and thrombocytopenia (low platelets and white blood cells). Pain may be relieved by NSAIDs, and there may be a fever. The first symptoms of MM may involve the skin, causing skin lesions such as plaques and itching, rash, and erythema (redness) or hyperpigmentation (barking redness).
Multiple myeloma is a cancer of bone and marrow, characterized by the rapid proliferation of plasma cells, the abnormal accumulation of such cells, and the deposition of new bone. About 1.4% of the US population is currently diagnosed with multiple myeloma. It typically arises after age 60 and affects approximately 1 man for every 1000 women.\n
Multiple myeloma cannot be cured for most patients. The number of patients that are considered to be curable varies widely but patients in complete remission have been recorded as having a very low risk for relapse. However, patients who become symptomatic after a period of remission may have a relatively high risk for dying.
There have been two main clinical trials: DAR-301 (daro-301) and BOLD-3 (BOR-23054). DAR-301 (daro-301), which is already approved with FDA, failed to meet its primary endpoint (durable response in patients with multiple myeloma following at least five cycles of treatment with bortezomib therapy, with at least 90% of respondents achieving ≥ 60% PFS [progression-free survival, time to disease progression, or death].
Dar+ patients most often present with advanced disease that is inextremately refractory to other treatments (in particular, bortezomib). In these patients, it can achieve ORR even in the presence of progressive disease, suggesting that darimumab may be more efficacious through alternative mechanisms.
Multiple myeloma is often an incurable illness, and treatment options for the disease are limited. There is still little understanding of the clinical features and prognosis of the disease, as well as the impact of its treatment. Many of the challenges facing clinicians involve obtaining accurate pre-treatment information on disease trajectory and the extent of disease. It is for this reason that clinicians are not always able to offer a more realistic appraisal of the disease in their patients, in particular when diagnosing the rare patients at an earlier stage.
Results of this trial could not be powered to detect a significant difference in treatment response or overall rate of survival. However, analysis of secondary endpoints suggests that daratumumab is well tolerated, with a low incidence of serious infections and an excellent rate of antibody-mediated adverse events.
Daratumumab was well tolerated and was associated with no significant improvements in disease response or survival in people with multiple myeloma. Prospective trials are required to validate these findings and enable a recommendation to be made regarding daratumumab for use in people with multiple myeloma.