If a patient with multiple myeloma (MM) experiences a suboptimal response to initial treatment, clinicians may choose to switch to a different agent class with the aim of response intensification, according to study results published The Lancet Haematology.

Researchers assessed response-adapted intensification with cyclophosphamide, bortezomib, and dexamethasone compared with no intensification in patients with newly diagnosed MM. They found that some patients may not respond to induction therapy but may benefit from response-adapted intensification.

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The researchers conducted an open label, randomized, phase 3, adaptive-design trial at 110 National Health Service hospitals in the United Kingdom. Patients were randomly assigned to 3 arms: induction treatment, intensification treatment, and maintenance treatment. All patients were 18 years or older and had symptomatic or nonsecretory, newly diagnosed MM and had achieved partial or minimal response after completing induction therapy with cyclophosphamide, dexamethasone, and thalidomide or lenalidomide. Of the 1217 patients who achieved partial or minimal response, 583 (48%) were assigned to the intensification group.

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Patients were stratified by allocated induction treatment, response to induction treatment, and medical center. Primary end points were progression-free (PFS) and overall survival (OS) and were assessed from intensification randomization to data cutoff.

Median PFS was 30 months in the intensification group and 20 months in the maintenance group (hazard ratio [HR], 0.60; P <.0001) after a median follow-up of 29.7 months. The rates of 3-year OS were similar between the intensification and maintenance groups (77.3% vs 78.5%; HR, .098; P =.93).

The most common grade 3 or 4 adverse events in the intensification group were hematologic, with 7% of patients experiencing neutropenia, 7% experiencing thrombocytopenia, and 3% experiencing anemia. In the intensification group, no deaths were determined to be treatment-related.

The researchers concluded that the manageable safety profile of this intensification strategy, as well as the improvement seen in PFS, support further investigation of response-adapted approaches.


1.     Jackson GH, Davies FE, Pawlyn C, et al. Response-adapted intensification with cyclophosphamide, bortezomib, and dexamethasone versus no intensification in patients with newly diagnosed multiple myeloma (Myeloma XI): a multicentre, open-label, randomised, phase 3 trial [published online October 14, 2019]. Lancet Haematol. doi:10.1016/S2352-3026(19)30167-X