Multiple Myeloma Treatment Information for Healthcare Professionals

Refractory Plasma Cell Neoplasm

There are two main types of refractory myeloma patients: primary refractory patients who never achieve a response and progress while still on induction chemotherapy; and secondary refractory patients who do respond to induction chemotherapy, but do not respond to treatment after relapse. The primary group may respond to high-dose chemotherapy and autologous stem cell rescue.^1,2

Of the patients who do not achieve a response to induction chemotherapy, a subgroup of about 10% have stable disease and enjoy a survival prognosis that is as good as that for responding patients.^3,4 When the stable nature of the disease becomes established, these patients can discontinue therapy until the myeloma begins to progress again. Others with primary refractory myeloma and progressive disease require a change in therapy; the choices have been reviewed.^4,5

A preliminary report on thalidomide suggests anti-tumor activity with minimal hematologic toxic effects.⁶ Further clinical trials are underway.

For patients who respond to their initial therapy, the myeloma growth rate, as measured by the M-protein doubling time, increases progressively with each subsequent relapse and remission durations become shorter and shorter. Marrow function becomes increasingly compromised as patients develop pancytopenia and enter a refractory phase; occasionally the myeloma cells dedifferentiate and extramedullary plasmacytomas develop. The myeloma cells may still be sensitive to chemotherapy, but the regrowth rate during relapse is so rapid that progressive improvement is not observed. At this stage of the disease, high- dose glucocorticoids may be the best approach.^7,8 High-dose chemotherapy with growth factor support is being evaluated in these refractory situations.⁹ Less myelosuppressive regimens can also be used as second- or third-line therapy.¹⁰

References:

1. Barlogie B, Southwest Oncology Group: NCI HIGH PRIORITY CLINICAL TRIAL --- Phase III Randomized Study of Melphalan/Total Body Irradiation with Peripheral Blood Stem Cell Rescue vs VBMCP (Vincristine/Carmustine/Melphalan/Cyclophosphamide/Prednisone) Following Standard Induction for Previously Untreated Symptomatic Multiple Myeloma, with Further Randomization for Major Responders to Interferon alfa vs Observation (Summary Last Modified 12/1999), SWOG-9321, clinical trial, active, 01/15/1994.
2. Attal M, Harousseau JL, Stoppa AM, et al.: A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. New England Journal of Medicine 335(2): 91-97, 1996.
3. Bergsagel DE: Use a gentle approach for refractory myeloma patients. Journal of Clinical Oncology 6(5): 757-758, 1988.
4. Bergsagel DE: Chemotherapy of myeloma. In: Malpas JS, Bergsagel DE, Kyle RA, et al. eds.: Myeloma: Biology and Management. 2nd ed., Oxford, England: Oxford University Press, 1998, pp 269-302.
5. Buzaid AC, Durie BG: Management of refractory myeloma: a review. Journal of Clinical Oncology 6(5): 889-905, 1988.
6. Singhal S, Mehta J, Eddlemon P, et al.: Marked anti-tumor effect from anti-angiogenesis (AA) therapy with thalidomide (T) in high risk refactory multiple myeloma (MM). Blood A-1306: 318a, 1998.
7. Alexanian R, Barlogie B, Dixon DO: High-dose glucocorticoid treatment of resistant myeloma. Annals of Internal Medicine 105(1): 8-11, 1986.
8. Norfolk DR, Child JA: Pulsed high dose oral prednisolone in relapsed or refractory multiple myeloma. Hematological Oncology 7(1): 61-68, 1989.
9. Dimopoulos MA, Weber D, Kantarjian H, et al.: HyperCVAD for VAD-resistant multiple myeloma. American Journal of Hematology 52(2): 77-81, 1996.
10. Brugnatelli S, Riccardi A, Ucci G, et al.: Experience with poorly myelosuppressive chemotherapy schedules for advanced myeloma. British Journal of Cancer 73(6): 794-797, 1996.

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