Differences in Patterns of Treatment and Outcome Among Patients with Relapsed Refractory Myeloma From United States, Europe and Asia,

Treatment patterns of multiple myeloma (MM) vary across the globe, mostly dictated by the availability and patient access to different drug therapies. The outcomes of patients with MM, especially relapsed myeloma can be significantly affected by the availability of newer treatments, as well as potential biological differences related to ethnicity. We have previously shown that the outcome of patients relapsing after therapy with bortezomib (Bz) and one or more of the IMiDs remain poor with the currently available treatments and represent a difficult group of patients to treat. We undertook the current analysis on a set of patients from United States, several European countries and South Korea.

We designed a multicenter, retrospective study that enrolled 294 patients with relapsed MM, from 14 sites (122 from Europe, 107 from US, and 65 from Korea). Patients were refractory to Bz, defined as no response to prior Bz-containing regimen or disease progression within 60 days of a Bz-containing regimen. Patients were also relapsed, refractory, intolerant, and/or ineligible, to treatment with an IMiD (thalidomide or lenalidomide). The date patients satisfied the above entry criteria was defined as time zero (T₀). Clinical and laboratory data from diagnosis and individual relapses were collected along with details of all MM drug therapies before and after T₀. Responses were assessed by IMWG or EBMT criteria. The goal of the study was to compare the characteristics of patients who satisfy the above inclusion criteria, the therapies employed prior to and after T₀ and clinical outcome among these patients from different parts of the world.

The mean (median, range) time to reaching T₀ from diagnosis was 4.5 (4.0, 12.8), 4.2 (3.2, 18.6), and 3.2 (2.8, 9.6) years from diagnosis for patients from US, Europe and Korea, respectively, P=0.021. The mean (median, range) number of therapies for the three groups were 8 (8, 13), 4 (4, 10), 5 (4, 7), respectively; P<0.001. The response rates (>=PR) to the initial therapy at diagnosis were 56%, 77% and 49% respectively for the US, European and Korean cohorts. Overall 220 patients had at least one therapy after T₀, and 114 (52%) had a novel agent (Bz, len or thal) containing regimen as their first treatment after T₀. Patients in US were more likely to receive additional therapies after the first post-T₀ therapy; 62%, 32%, and 12% of patients from US, Europe and Korea, respectively, began a second post-T₀ regimen within 2 years following time zero. The median number of therapies post T₀ was 2, 1, and 1 for patients in US, Europe and Korea respectively. The response rates to the first regimen after T₀ were 15%, 33% and 19% for the US, European and Korean cohorts, and were similar between those receiving a regimen with one of the novel drugs compared to rest. Patients younger than 60 years and those with prior transplants were more likely to respond to post T₀ regimens. The median time to progression or death from T₀was similar for the three patient cohorts, 5 months (Figure 1A). The median overall survival (95% CI) from T₀ was 13 months (10, 16), 7 (5,9) and 8 (4,9) respectively for the US, European and Korean cohorts (Figure 1B). Conventional prognostic factors, especially the ISS stage was predictive of OS post T₀. Additionally, presence of extramedullary disease was associated with a shorter overall survival.

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The results of the current study demonstrate significant differences between different parts of the world in terms of the treatment patterns both in the setting of initial therapy as well as treatment of relapsed disease. Patients in the US were more likely to receive multiple regimens both before and after T0. This is likely a reflection of increasing numbers of new drugs that have gone into clinical trials and thus enhancing options. The study further highlights the poor outcome of patients who have relapsed after the new drugs, irrespective of the geographical location.

Kumar:Merck: Consultancy, Honoraria; Genzyme: Consultancy; Celgene: Consultancy. Richardson:Millennium: ; Celgene: ; Johnson & Johnson: ; Novartis: ; Bristol Myers Squibb:. Moreau:Millennium Pharmaceuticals, Inc.: Advisory board, Honoraria; Janssen: Advisory board, Honoraria. Sonneveld:Millennium Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding. Siegel:Merck: Honoraria; Millenium: Honoraria, Research Funding, Speakers Bureau. San Miguel:Janssen-Cilag: Honoraria; Celgene: Honoraria. Palumbo:celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Durie:Celgene: Membership on an entity's Board of Directors or advisory committees.