Guidelines on the Diagnosis and Management of Multiple Myeloma

8. Management of Relapsed and Refractory Disease

Primary Refractory Disease

There is a lack of evidence from randomised controlled trials on the optimum approach to treating primary refractory disease. Patients refractory to alkylating agents may respond well to VAD-type regimens (Barlogie et al, 1984). Conversely, younger patients treated with VAD as primary therapy who fail to respond prior to planned SCT may still respond to high-dose melphalan (Vesole et al, 1999; Rajkumar et al, 1999).

For the majority of patients in this category, attempts to influence the course of the disease with chemotherapy will be, by definition, unsuccessful so that the focus of management for these patients should be on control of symptoms and maximising the quality of their survival.

Relapsed / progressive disease

Since almost all patients with myeloma will relapse the overall management strategy should include plans to treat relapse. In most cases the therapeutic objectives will still be to achieve disease control, ameliorate symptoms, improve quality of life and prolong survival. Early relapse carries a poor prognosis and is likely to respond poorly to most chemotherapy. Patients who relapse or progress after a long stable plateau phase are likely to respond well to further treatment.

Possible treatment regimens for relapsed myeloma therefore include no further anti-neoplastic treatment, repeating initial chemotherapy or high-dose therapy. There are also a number of novel and experimental therapies available.

Current options include:

• no further anti-neoplastic treatment
• melphalan with or without prednisolone
• C-weekly
• combination chemotherapy
• VAD and similar regimens with or without resistance modification agents (e.g. PSC 833)
• oral idarubicin alone or in combination
• high-dose dexamethasone
• high-dose therapy with stem cell transplantation
• thalidomide
• hemibody irradiation

Available evidence suggests that if the patient was initially treated with MP and achieved stable plateau MP is appropriate treatment as a further response can be achieved in 50% patients (Belch et al, 1988).

Patients who have been treated previously with alkylating agents may respond well to VAD or related regimens (Barlogie et al, 1984) or an idarubicin-based regimen (Cook et al, 1996; Parameswaran et al, 2000).

HDT and stem cell transplantation may be considered in patients who have not had a prior stem cell transplant. A second HDT may also be appropriate in selected patients who relapse after an initial autograft (those with a low b₂-microglobulin, one prior transplant and late relapse) (Tricot et al, 1995(b); Mehta et al, 1998; Lokhorst, 1999).

Steroids alone may be useful in patients at second or later relapse or in patients in whom chemotherapy is contra-indicated (Alexanian et al, 1986).

Thalidomide has been recently shown to produce responses in at least 30% of relapsed/refractory patients (Singhal et al, 1999; Juliusson et al, 2000; Barlogie et al, 2001). Higher response rates have been observed with the combination of thalidomide and dexmethasone (Dimopoulos et al, 2001; Palumbo et al, 2001). On current evidence it is reasonable to offer thalidomide to relasped/refractory patients pending the results of clinical trials which are currently evaluating the role of thalidomide at earlier stages of the disease. A position paper from the UK Myeloma Forum on the use of thalidomide in myeloma is in preparation and will be available on the UKMF and BSH/BCSH web-sites (anticipated late 2001).

Double hemi-body irradiation is useful in patients with widespread bone pain and in those who are refractory to chemotherapy and steroids (Singer et al, 1989). Caution is required as it can cause significant myelosuppression.

Recommendations:

 

<< 7. Bisphosphonates

9. Management of Patients With Renal Failure >>