Three-drug versus two-drug induction therapy regimens for patients with transplant-eligible multiple myeloma

Background: Current definition of multi-hit multiple myeloma (MM) is based upon the number of high-risk cytogenetic abnormalities (CA). But we may overlook the influence of standard-risk CA and different concurrent patterns. In fact, standard-risk t(11;14) and del(13q) may bring extra danger when concurrent with other CA. And the concurrency of two secondary CA may do more harm to patients than that of one secondary CA with one primary CA. This study is to answer whether CA number or pattern exert an impact on outcomes of MM patients. Methods: This study was carried out based on the prospective, non-randomized clinical trial BDH 2008/02. 537 MM patients with complete cytogenetic data were enrolled, of whom 64% (341/537) patients were treated with bortezomib-based three-drug induction therapy, and the remaining patients with thalidomide-based therapy. Autologous stem cell transplantation (ASCT) was recommended post induction therapy in transplant-eligible patients, and all patients received maintenance therapy for two years. CA were divided into primary CA [pCA: any type of IgH breakage], and secondary CA [sCA: del(17p), del(13q), gain(1q) (≥3 copies)] Results: In the era of novel agents, patients with pCA only did not have outcomes different from those patients without any FISH abnormality. Patients with s1 CA or s1+p CA had hazard ratio for PFS or OS of 1.5-2.0. Patients with s2 CA or s2+p CA had hazard ratio for PFS or OS of 2.0-3.0. Patients with concurrent del(13q), del(17p) and gain(1q) (s3 CA) had hazard ratio for PFS of 3.11 and for OS of 3.00. Patients with s3+p CA had hazard ratio for PFS of 4.65 and for OS of 6.16. Based on these results, we divided patients into four subgroups: no CA or only pCA, s1 CA in the presence or absence of pCA, s2 CA in the presence or absence of pCA, and s3 CA in the presence or absence of pCA. Both the PFS and OS decreased in a stepwise fashion with the accumulation of CA (Figure 1). Therefore, we defined double-hit MM as any one sCA in the presence or absence of pCA. Triple-hit MM referred to two sCA plus pCA or not, and quadra-hit MM referred to three sCA plus pCA or not. Furthermore, we confirmed the prognostic independence of CA pattern in the multivariant analysis with International Staging System (ISS) and LDH (Table 1). Conclusion: In this study, we found that the primary CA as a whole lost its adverse effect when treated by bortezomib-based regimens. CA subtype conferred a prognostic value. In details, secondary CA imposed an accumulative risk to patients. For the first time, we indicated that double-hit or triple-hit MM should be defined upon the number of secondary CA. This definition coincides with the "Two-Hit" theory of cancer causation and fits well with MM evolution model. The prognostic significance of CA pattern needs validation in further prospective trials. Disclosures No relevant conflicts of interest to declare.

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Three-drug versus two-drug induction therapy regimens for patients with transplant-eligible multiple myeloma

10.1002/14651858.cd010602 ◽

2013 ◽

Author(s):

Mohamed Kharfan-Dabaja ◽

Taiga Nishihori ◽

Tea Reljic ◽

Mehdi Hamadani ◽

Rachid Baz ◽

...

Keyword(s):

Multiple Myeloma ◽

Induction Therapy ◽

Drug Induction

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Treatment Disparities in Minority Groups with Multiple Myeloma at a Large Safety-Net Hospital

Blood ◽

10.1182/blood-2018-99-118472 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4864-4864

Author(s):

Michael Dennis ◽

Diana Cirstea ◽

Asaf Maoz ◽

Adam Lerner ◽

Ami K. Patel ◽

...

Keyword(s):

Multiple Myeloma ◽

Ethnic Groups ◽

Induction Therapy ◽

Minority Groups ◽

Safety Net ◽

First Year ◽

Cell Transplant ◽

Induction Regimen ◽

Drug Induction ◽

Racial Ethnic

Abstract Background: Outcomes in multiple myeloma (MM) have improved in recent years, but disparities among racial-ethnic groups persist (Costa, 2017; Ailawadhi, 2012; Waxman, 2010). Differences in disease biology, treatment modalities, and access to care are likely explanations for these disparities. Currently the preferred induction therapy for MM is a three-drug regimen, such as bortezomib/cyclophosphamide/dexamethasone (VCD), bortezomib/lenalidomide/dexamethasone (VRD) or carfilzomib/pomalidomide/dexamethasone (KPd). This is often followed by high-dose melphalan with autologous stem cell transplant (HDM/SCT) and maintenance therapy. Older or frail adults may not tolerate this three-drug approach or HDM/SCT. Two-drug regimens without HDM/SCT are acceptable options in these groups. This retrospective study was designed to explore the utilization of preferred induction therapy and HDM/SCT across racial-ethnic groups at Boston Medical Center. Results: One hundred sixty-eight patients with MM were treated at our institution between 2004 and 2017. Sixty-six percent were non-Hispanic Black (NHB), 20% were non-Hispanic White (NHW), and 14% were Hispanic. The average age was 63 years and 56% of the population was male. There was no significant difference in age or sex between the NHB, NHW, and Hispanic groups. Only 83 patients (49%) received a three-drug induction regimen. Forty-six (51%) were < 65 years old, while 37 (48%) were ≥ 65 years old. The utilization of standard induction therapy was significantly different among racial-ethnic groups < 65 years old. Thirteen NHW patients (76%) received triplet induction therapy, compared to only 10 Hispanics (63%) and 23 NHB patients (40%) (p=0.02). A similar trend was observed in regards to treatment with HDM/SCT within the first year after diagnosis for patients age < 65 years and triplet therapy in patients undergoing HDM/SCT (any age), although these trends did not reach statistical significance (47% NHWs, 31% Hispanics, and 28% NHBs, p=0.31 and 91% NHWs, 78% Hispanics, and 58% NHBs, p=0.11 respectively). There were no significant differences among groups age ≥ 65 years in regards to triplet induction therapy, HDM/SCT within the first year, or HDM/SCT any time after diagnosis. The median time to HDM/SCT and overall survival were not significantly different between racial-ethnic groups, regardless of age above or below 65 years. Conclusion: NHB and Hispanic patients less than 65 years old are less likely to receive a standard three-drug induction regimen. There is also a trend towards fewer patients receiving HDM/SCT in the first year after diagnosis among these groups compared to NHW patients. Our study did not confirm a survival benefit in NHB patients under age 65, which has been reported in prior studies (Fillmore, 2018; Waxman, 2010). The lack of benefit seen in this study could be related to lower rates of three-drug induction therapy and HDM/SCT in the NHB group. Further research is needed to explore patient co-morbidities, socioeconomic factors, and physician biases to determine why minority groups have less utilization of standard therapies. Table. Table. Disclosures No relevant conflicts of interest to declare.

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