The Time Required To Achieve Complete Remission (CR) during Intensive Therapy on Total Therapy 2 Does Not Influence Event Free Survival (EFS), While Improvement in Quality of Response with Ongoing Treatment Clearly Does.

Tricot, Guido; Reiner, Maureen; Zangari, Maurizio; van Rhee, Frits; Anaissie, Elias; Milner, Teresa; Barlogie, Bart

doi:10.1182/blood.V106.11.1157.1157

Abstract

In acute leukemia and intermediate/high grade lymphoma it is important to achieve a CR as early as possible. The aim of the study was to evaluate if the same is true in myeloma treated with intensive therapy including tandem transplants (Tx-1; Tx-2). A total of 668 patients were enrolled on our Total Therapy 2 protocol, which randomized patients upfront to intensive therapy with or without thalidomide. The protocol consisted of 4 induction cycles followed by tandem transplants, 1 year of consolidation chemotherapy and maintenance therapy with dexamethasone pulsing every 3 months for 1 year and interferon-α, if tolerated. This study is limited to the 570 patients who received at least one transplant. CR was defined as absence of serum and urine M-protein with negative immunofixation electrophoresis and < 5% bone marrow plasma cells. EFS analyses were performed using Kaplan-Meier plots and log rank statistics to compare different groups. A 1 year landmark after Tx-1 was employed to compensate for guaranteed time of CR patients. Prior to Tx-1 89 patients (16%) were in CR, 111 in near CR (nCR), 110 in partial remission (PR) and 260 in < PR. After Tx-1, 170 (30%) achieved CR, 159 nCR, 116 PR and 125 < PR. The ultimate best response was CR in 319 patients (56%), nCR in 134, PR in 68 and < PR in 49. EFS of patients ultimately achieving CR was similar for those who were either in CR, nCR, PR or < PR prior to Tx-1 (p=0.47; Fig 1a). Patients in PR prior to Tx-1, but ultimately achieving CR or nCR faired considerably better than those who remained in PR (p=0.003 Fig 1b). Similarly, EFS of patients ultimately achieving CR was comparable for those who were either in CR, nCR, PR or < PR prior to Tx-2 (p=0.53). The same observations were made for both patients randomized to thalidomide or no thalidomide, or with and without baseline metaphase cytogenetics. With a median follow-up of 3 year after Tx-1 no difference in EFS was seen relative to the timing of achievement of CR. However, improvement of quality of response with further therapy resulted in a significant increase in EFS, strongly suggesting additional benefit from the second transplant and consolidation chemotherapy.

1a