Single autologous bone marrow or peripheral stem cell transplant

While some prospective randomized trials showed improved survival for patients who received autologous peripheral stem cell or bone marrow transplant after induction chemotherapy compared with chemotherapy alone,[25,85-87][Level of evidence A1] other trials have not shown any survival advantage.[88-93][Level of evidence A1]

In a prospective randomized trial (NCT01208662), 722 patients aged 65 years or younger with newly diagnosed multiple myeloma received either VRd for three cycles followed by autologous SCT consolidation and two more cycles of VRd or VRd alone for eight cycles. Both groups received maintenance lenalidomide given continuously in the absence of disease relapse or unacceptable side effects.[94] At relapse, patients who received VRd only (without autologous SCT) were re-induced and offered transplant if they were still responding.

In a prospective randomized trial (NCT01208662), 722 patients aged 65 years or younger with newly diagnosed multiple myeloma received either VRd for three cycles followed by autologous SCT consolidation and two more cycles of VRd or VRd alone for eight cycles. Both groups received maintenance lenalidomide given continuously in the absence of disease relapse or unacceptable side effects.[94] At relapse, patients who received VRd only (without autologous SCT) were re-induced and offered transplant if they were still responding.

With a median follow-up of 76.0 months, the median PFS was shorter for patients in the nontransplant arm (42.0 months) than for patients in the transplant arm (67.5 months) (HR, 1.53; 95% CI, 1.23–1.91; P < .001).[94][Level of evidence B1]

In a prospective randomized trial (NCT01208662), 722 patients aged 65 years or younger with newly diagnosed multiple myeloma received either VRd for three cycles followed by autologous SCT consolidation and two more cycles of VRd or VRd alone for eight cycles. Both groups received maintenance lenalidomide given continuously in the absence of disease relapse or unacceptable side effects.[94] At relapse, patients who received VRd only (without autologous SCT) were re-induced and offered transplant if they were still responding.

The 5-year OS rate was not significantly different: 79.2% for patients in the nontransplant arm versus 80.7% for patients in the transplant arm (HR, 1.10; 95% CI, 0.73–1.65; P > 0.99).

In a prospective randomized trial (NCT01208662), 722 patients aged 65 years or younger with newly diagnosed multiple myeloma received either VRd for three cycles followed by autologous SCT consolidation and two more cycles of VRd or VRd alone for eight cycles. Both groups received maintenance lenalidomide given continuously in the absence of disease relapse or unacceptable side effects.[94] At relapse, patients who received VRd only (without autologous SCT) were re-induced and offered transplant if they were still responding.

Rates of grade 3 or 4 hematologic adverse events were significantly higher in the transplant arm (41.9%) than in the nontransplant arm (26.1%) (P < .001). Acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) were only reported in the transplant arm (10 cases).

In a prospective randomized trial (NCT01208662), 722 patients aged 65 years or younger with newly diagnosed multiple myeloma received either VRd for three cycles followed by autologous SCT consolidation and two more cycles of VRd or VRd alone for eight cycles. Both groups received maintenance lenalidomide given continuously in the absence of disease relapse or unacceptable side effects.[94] At relapse, patients who received VRd only (without autologous SCT) were re-induced and offered transplant if they were still responding.

Only 28% of patients who received VRd originally received autologous SCT at any time after the end of study treatment.

Three meta-analyses of almost 3,000 patients showed no survival advantage.[22,95,96][Level of evidence A1]

A meta-analysis was performed for all randomized clinical trials conducted between 2000 and 2021 that compared up-front autologous SCT with standard-dose therapy/consolidation. A total of 3,307 citations were screened: six trials were selected for PFS analysis and four trials were selected for OS analysis (2,959 patients).[97]

A meta-analysis was performed for all randomized clinical trials conducted between 2000 and 2021 that compared up-front autologous SCT with standard-dose therapy/consolidation. A total of 3,307 citations were screened: six trials were selected for PFS analysis and four trials were selected for OS analysis (2,959 patients).[97]

With a median follow-up of 3.1 to 7.8 years, patients with high-risk cytogenetics (t(4;14), t(14;16), and/or del(17p)) had a significant OS benefit from autologous SCT versus standard-dose therapy (HR, 0.66; 95% CI, 0.45–0.97; P = .03).[97][Level of evidence A2] No survival benefit was seen for patients with standard-risk cytogenetics.

A meta-analysis was performed for all randomized clinical trials conducted between 2000 and 2021 that compared up-front autologous SCT with standard-dose therapy/consolidation. A total of 3,307 citations were screened: six trials were selected for PFS analysis and four trials were selected for OS analysis (2,959 patients).[97]

Patients with high-risk disease (approximately 20% of the total) showed a significant PFS benefit from autologous SCT versus standard-dose therapy (HR, 0.52; 95% CI, 0.33–0.83). Patients with standard-risk disease also showed a PFS benefit from autologous SCT (HR, 0.65; 95% CI, 0.56–0.76).[97]