Dr Sonia Zweegman and Prof Marivi Mateos talk to ecancertv at IMW 2013.
Defining an elderly multiple myeloma (MM) patient can be difficult. Currently we use chronological age, defined as those aged 65 years or older. A second age group is those aged 75 years and older, who tend to be more unfit or frail. However, the use of biological age through geriatric assessment should be considered in the future.
The objective of treatment in elderly MM patients has changed with the arrival of novel therapies. In the past, complete remission (CR) was not a viable objective. However, with the introduction of immunomodulatory drugs and proteasome inhibitors, CR rates have significantly increased. Studies indicate that elderly patients who achieve CR have a prolongation of progression free survival (PFS) and overall survival (OS).
Based on these results, the objective of treatment in elderly patients is now CR. It is possible to evaluate response to treatment through immunophenotypic assessment.
The depth of response is important but toxicity also needs to be taken into consideration when treating elderly patients. A balance is needed between a high CR and the degree of toxicity that the patient can tolerate in order to continue treatment. In Europe an alkylating-based regimen combined with a novel agent is frequently considered, in particular thalidomide and bortezomib.
These regimens have not been compared head to head, so it is difficult to ascertain which one is superior. However, the MPV (melphalan-prednisone-bortezomib) VISTA trial showed a significant improvement in OS of around 13 months. In contrast, the meta-analysis of the MPT (melphalan-prednisone-thalidomide) trials, showed an OS of less than 6 months. Based on these results, MPV is considered a good first line regimen and MPT is a good second option. In order to minimise toxicity in elderly patients, a weekly schedule for MPV with prolonged maintenance therapy was investigated.
This resulted in a significantly reduced peripheral neuropathy rate versus that observed in the VISTA trial. Gastrointestinal toxicity and discontinuation rate were also both significantly reduced. The efficacy was maintained and even improved with maintenance therapy. These results were reproduced in an Italian trial conducted by Dr Palumbo.
Another important consideration is the route of administration. The subcutaneous formulation has been found to be noninferior to the intravenous formulation. Interestingly, it has also been shown to result in significantly reduced peripheral neuropathy rates. Therefore, an optimal way to treat elderly patient with MM is to offer subcutaneous MPV on a weekly schedule as six induction cycles followed by maintenance therapy. However, maintenance therapy cannot be given outside of clinical trials. Therefore, in clinical practice the first cycle consists of bortezomib twice a week, followed by 8 additional cycles in which bortezomib is given just once a week.
Prolongation of therapy in elderly patients is important to ensure PFS is as long as possible as re-treatment may not be an option in these patients. With regard to MPT, this is more challenging. Peripheral neuropathy is more prevalent with a longer period of administration and patients frequently discontinue thalidomide maintenance therapy because it was not feasible for many of them. Cytogenic analysis prior to treatment with thalidomide is necessary to establish those at risk of harm. In patients with low levels of risk and in whom thalidomide is feasible, maintenance therapy can be continued. For lenalidomide, the MM015 trial demonstrated no PFS benefit without maintenance. In addition, the dose of lenalidomide was limited in patients over 75 years of age because of toxicity.
Therefore, a 'soft' start is recommended for this treatment. In terms of preference of an alkykating agent versus corticosteroid, data from the French MM020 trial, which is comparing MPT with a combination of lenalidomide and dexamethasone, is eagerly awaited and will provide an answer to this question.
Outside clinical trials, current clinical practice for the management of elderly MM patients in Europe is MPV as first line treatment, with MPT as a valuable alternative.
This programme has been supported by an unrestricted educational grant from Janssen Pharmaceutica (A Johnson & Johnson Company).