MULTIPLE MYELOMA
Front-Line Therapy
The speaker for this topic was Antonio Palumbo, MD from the University of Torino in Torino, Italy.

Over the last two decades three distinct groups of patients with newly diagnosed multiple myeloma have emerged. They are young patients (<65 years of age), elderly fit patients (≥ 65 years), and the elderly unfit patients (≥ 65 years) with concomitant medical illnesses. Improvements in our prognostic ability and in treatment options now make it possible to make appropriate therapeutic choices for patients in each group.

Several factors have contributed to our ability to better define these patient groups. First, increasing life span has resulted in an increased number of patients ≥65 years of age (the elderly group). Second, improved techniques for autologous stem cell transplantation (ASCT), improved supportive care options, and a group of novel anti-myeloma agents with impressive efficacy have resulted in improved survival for myeloma patients who are candidates for ASCT. These advances have made ASCT a viable option as front-line therapy for young patients and for some fit elderly patients as well. The final contributing factor is the influence of cytogenetics and beta-2-microglobulin (B₂MG) in defining risk and predicting outcomes in myeloma patients. Those with FISH(-), B₂MG <4 and some with del 13, B₂MG <4 have a 50% 5-year survival (S) of 80%. Those with FISH(-), B₂MG >4, del 13, B₂MG >4 and some with 4;14 or 17p, B₂MG <4 have a 50% 5-year S. All patients with 2 abnormal risk factors (4;14, 17p and B₂MG >4) have a poor prognosis even after tandem ASCT.

After that background information, Dr. Palumbo discussed his recommendations for management of the three patient groups. He stated that when you see a young patient, you generally think about ASCT and induction regimens used with that therapy. Lenalidomide (Len) + low-dose (LD) Dex has been proven to be more efficacious and less toxic (fewer severe A/Es and far fewer deaths) than Len + high-dose (HD) Dex – Len + LD-Dex is effective alone and as an induction therapy prior to ASCT. It is now proven in several trials to result in successful stem cell harvest in 97% to 100% of patients. Other induction regimens are Vel/Dex (bortezomib + Dex) and VTD (bortezomib + thalidomide + Dex).

The elderly fit patient group (≥65 years) certainly can be ASCT candidates with Len + LD-Dex or PAD (bortezomib + pegylated doxorubicin + Dex) induction. Non-ASCT patients in this group can benefit from regimens such as MPT (melphalan + prednisone + thalidomide) used in the IFM and Nordic Study Trials. VMP (bortezomib, melphalan + prednisone) was very effective in the VISTA registration trial.

The elderly unfit patients with concomitant illness should be evaluated perhaps for one of the non-ASCT regimens, but most will end up on best supportive care which is appropriate.

The speaker passed on two “clinical pearls” as take home messages:

• Aspirin is challenging low molecular weight heparin (LMWH) as the preferred prophylactic agent for thromboembolic events in myeloma patients.
  
• New effective regimens should be used early in the course of multiple myeloma.