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Drug therapy

High-dose chemotherapy with autologous stem cell support (HDT with SCS) can prolong survival in younger patients. In some cases, an allogeneic stem cell transplantation may be appropriate.

Allogeneic stem cell transplantation has curative potential and can provide a very long remission in those with a suitable donor. However, the risk of fatal or troublesome side effects is so substantial that the treatment is rarely used. Allogeneic stem cell transplant with reduced pre-treatment is under evaluation in multiple studies and is so far not established in the primary treatment.   

Patients who cannot be offered high-dose treatment are given chemotherapy to improve quality of life and prolong survival.

Chemotherapy for patients appropriate for HDT with SCS

First-line treatment is cyclophosphamide and dexamethasone x 2–3 before stem cell mobilization and stem cell harvesting.

It is now clear that combinations with bortezomib, thalidomide or lenalidomide as primary treatment give better response before HMAS and prolonged time to progression of the disease. We do not know, however, what this means in terms of a satisfying result of treatment in case of progression, or for the total survival. If the patient cannot be included in a study, until further documentation is available, a regimen of cyclophosphamide-dexamethason in combination with either bortezomib or thalidomide will usually be chosen. Ordinarily, 2-3 courses are given before mobilization/harvesting of stem cells.

Chemotherapy for patients not appropriate for HDT with SCS

For patients who are not appropriate for HDT with SCS, the goal of treatment is to achieve a response with minimal toxicity related to treatment. Recommended primary treatment is melphalan and prednisolone (MP) with the addition of thalidomide according to individual consideration (MP-T). The combinations MP-bortezomib and MP-lenalidomide are under are under evaluation in studies.  

Chemotherapy for patients with renal failure

The goal of treatment is primarily to achieve quick reduction of paraprotein and light chains with a regimen which can safely be used on patients with renal failure. HMAS is also considered for younger patients even if the renal failure does not improve. Thalidomide and possibly bortezomib can be taken in renal failure. 

Treatment for patients with refractory illness

  • The treatment schedule must be adapted for age, previous treatment, and clinical status.
  • In younger patients with refractory illness, the illness can be stabilized with second-line treatment. Where HMAS can be carried out, high-dose melphalan provides the best prognosis.
  • If possible, the patient should be included in a treatment study.

High-dose treatment with stem cell support (HDT with SCS)

  • HDT with SCS is today a part of the primary treatment strategy in newly diagnosed patients < 65 years with adequate general health status and good organ function. Treatment-related mortality is 1–2%. 
  • High-dose treatment with autologous stem cell support can be considered in patients > 65 years with good general health condition, however treatment benefit has not be documented. 
  • Conditioning with melphalan alone, without total-body radiation, is recommended. The dosage is usually 200 mg/m2, but the dosage should be reduced in elderly and patients with kidney failure.
  • Double HMAS is carried out under special circumstances where the result from initial HDT with SCS treatment is not satisfactory.

Allogeneic stem cell transplant

  • Patients up to 45 years who have responded to chemotherapy may be considered for myeloablative allogeneic stem cell transplantation with an HLA-compatible sibling donor. The patient should ideally be included in a treatment study. 
  • Non-myeloablative allogeneic stem cell transplantation may be considered in patients up to 65–70 years with HLA-compatible sibling donor. This procedure should be preceded by HMAS, and the patient should be included in a treatment study.
  • Infusion of donor lymphocytes should be considered in patients with lasting or progressive illness after allogeneic transplantation. 
  • Non-myeloablative stem cell transplant with HLA-compatible unrelated donor may only be considered as part of a treatment study. Myeloablative conditioning is not recommended with unrelated donors. 

Interferon

Interferon has been used in the plateau phase together with conventional treatment in multiple studies but, thus far, there is no documented benefit. However, this does not exclude that some patients may benefit from it.

Disease progression

The treatment arrangement is adapted for each patient depending on:

  • time of relapse
  • age
  • previous treatment
  • bone marrow function
  • other clinical conditions

For the majority of patients with progression after a plateau phase achieved through treatment with melphalan/prednisolone as first-line treatment, the recommendation is to attempt retreatment with a melphalan-based regimen.

Thalidomide should be considered, often in combination with dexamethasone. If the patient does not respond to this treatment after 3 months, there is no benefit of continuing. There are no recommendations for duration of treatment if reponse is achieved.

Bortezomib combined with dexamethasone is also appropriate as second-line treatment in patients with acceptable general health status and organ function.

If possible, the treatment should be included in a treatment study.

Good supportive care is very important.

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