Newly diagnosed multiple myeloma patients

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Published: 2 Jul 2013
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Dr Alessandra Larocca - University of Torino, Italy

Data from a Phase 2 community based treatment study in fit, unfit and frail, elderly (>75 years of age), newly diagnosed multiple myeloma (MM) patients was presented at EHA 2013. Low dose, low intensity bortezomib based therapy was investigated to assess its safety and efficacy in these difficult to treat patients.

Treatment included nine 28-day cycles of bortezomib 1.3 mg/m2 subcutaneous (sc) on days 1, 8, 15 and 22 plus oral prednisone 50 mg every other day (VP) or VP plus oral cyclophosphamide 50 mg every other day (VCP) or oral melphalan 2 mg every other day (VMP) for 28 days, followed by maintenance with sc bortezomib every 2 weeks until progression.

Response rates ranged from 60-70% and discontinuation due to side effects ranged from 15-23% of patients. Responses were less pronounced and drug discontinuation was higher in frail patients versus fit and unfit patients, and was associated with lower survival outcomes. This study will help to identify which treatments may be appropriate in the different subgroups of elderly patients presenting with MM.

18th Congress of EHA

Newly diagnosed multiple myeloma (MM) patients

Dr Alessandra Larocca - University of Torino, Italy

What were the design and objectives of the phase II community based treatment study in frail, elderly, newly diagnosed multiple myeloma patients?

We designed this phase II three cohort multi-centre study to evaluate a low dose and low intensity bortezomib combination with subcutaneous bortezomib in a group of patients, very elderly, older than 75 years but the inclusion was open also to patients younger with comorbidities and so candidates for a lower dose intensity treatment. The trial consisted of three cohorts with three different schedules of treatment: one with bortezomib and prednisone, the second one with bortezomib, cyclophosphamide and prednisone and the third one with bortezomib, melphalan and prednisone. In each group we enrolled approximately fifty patients and the total number of patients enrolled was 152.

What outcomes were measured in this study?

Our primary endpoint was the assessment of overall response rate and the assessment of safety but overall was included the survival outcomes, the evaluation of survival outcomes.

What did the study show?

The results concerning best response, we observed an overall response rate slightly higher in the group of patients enrolled in the VMP cohort, so with melphalan based. But this was also slightly more toxic, for example we observed a slightly higher incidence of cardiac adverse events and infections and also the rate of bortezomib dose reduction and discontinuation of the drugs was slightly higher in the VMP. I define slight because it is a phase II non-randomised trial so we can observe only this data.

I think the most interesting result was concerning the definition of the three groups of patients because at baseline we performed a geriatric assessment including the evaluation of comorbidity with the Charlson index and the evaluation of functional and mental status of patients with the activity of daily living and instrumental activity of daily living. So, combining this geriatric assessment with the cut-off age of 80 years, we were able to identify three groups of patients that we defined as fit, unfit and frail. They showed a different overall response rate that was lower for the frail population and also the drug discontinuation was higher in the frail population. This translates with different survival outcomes because we observed a lower progression free survival and overall survival for frail patients as compared to the group defined as fit.

How will this data impact on the treatment of these types of patients?

We can confirm the important role of a geriatric assessment because with these methods we can select most appropriately the patients and so we could choose more appropriately the treatment. That could be different in these three groups of patients, fit, unfit and frail, because fit patients could be candidates for a full dose therapy, to receive the most of the treatment and unfit patients, probably it’s better that they receive a slightly reduced treatment but the frail population probably need a more palliative approach.