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. 2020 Aug 11;4(15):3509-3519.
doi: 10.1182/bloodadvances.2020002218.

Clinical characteristics and treatment outcomes of newly diagnosed multiple myeloma with chromosome 1q abnormalities

Nadine Abdallah  1 , Patricia Greipp  2 , Prashant Kapoor  1 , Morie A Gertz  1 , Angela Dispenzieri  1 , Linda B Baughn  2 , Martha Q Lacy  1 , Suzanne R Hayman  1 , Francis K Buadi  1 , David Dingli  1 , Ronald S Go  1 , Yi L Hwa  1 , Amie Fonder  1 , Miriam Hobbs  1 , Yi Lin  1 , Nelson Leung  1   3 , Taxiarchis Kourelis  1 , Rahma Warsame  1 , Mustaqeem Siddiqui  1 , John Lust  1 , Robert A Kyle  1 , Leif Bergsagel  4 , Rhett Ketterling  2 , S Vincent Rajkumar  1 , Shaji K Kumar  1
Affiliations

Clinical characteristics and treatment outcomes of newly diagnosed multiple myeloma with chromosome 1q abnormalities

Nadine Abdallah et al. Blood Adv. .

Abstract

A gain in chromosome 1q (+1q) is among the most common cytogenetic abnormalities in multiple myeloma (MM). It is unclear whether +1q is independently associated with decreased overall survival (OS). The objective of this study was to evaluate the impact of +1q on clinical characteristics, treatment response, and survival outcomes. We included 1376 Mayo Clinic patients diagnosed with MM from 2005 to 2018 who underwent fluorescence in situ hybridization testing at diagnosis with a panel including the +1q probe. A gain in 1q was found in 391 patients (28%) and was associated with anemia, hypercalcemia, high tumor burden, International Staging System (ISS) stage 3, high-risk (HR) translocations, and chromosome 13 abnormalities. There was no difference in overall response or deeper responses to proteasome inhibitor (PI)-, immunomodulatory drug (iMiD)-, or PI plus IMiD-based induction. Time to next treatment was shorter in patients with +1q compared with those without +1q (19.9 vs 27.7 months; P < .001). On univariate analysis, +1q was associated with increased risk of death (risk ratio [RR], 1.9; P < .001), and decreased OS was seen in all treatment groups. +1q was independently associated with decreased OS on multivariate analysis when other HR cytogenetic abnormalities, ISS stage 3, and age ≥70 years were included (RR, 1.5; P < .001). Gain of >1 copy of 1q was not associated with worse OS compared with gain of 1 copy (4.9 vs 4.3 years; P = .21). +1q was associated with high tumor burden, advanced disease stage, and HR translocations. It is independently associated with decreased OS, even in the setting of novel therapy and transplant.

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Conflict of interest statement

Conflict-of-interest disclosure: P.K. received research funding from Takeda Pharmaceuticals, Celgene, and Amgen. A.D. received research funding from Celgene, Millennium Pharmaceuticals, Pfizer, and Janssen and received a travel grant from Pfizer. M.A.G. served as a consultant for Millennium Pharmaceuticals and received honoraria from Celgene, Millennium Pharmaceuticals, Onyx Pharmaceuticals, Novartis, GlaxoSmithKline, Prothena, Ionis Pharmaceuticals, and Amgen. M.Q.L. received research funding from Celgene. N.L. serves on an advisory board for Takeda Pharmaceuticals. S.K.K. served as a consultant for Celgene, Millennium Pharmaceuticals, Onyx Pharmaceuticals, Janssen, and Bristol-Myers Squibb and received research funding from Celgene, Millennium Pharmaceuticals, Novartis, Onyx Pharmaceuticals, AbbVie, Janssen, and Bristol-Myers Squibb. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Response to first-line treatment. ORR and rate of VGPR or better to PI-, IMiD-, or PI plus IMiD–based first-line induction chemotherapy and transplantation in patients with and without +1q.
Figure 2.
Figure 2.
TTNT after first-line treatment. TTNT (months) in patients with (blue curve) and without +1q (red curve) among those who received PI- (A), IMiD- (B), and PI plus IMiD–based first line treatment (C).
Figure 3.
Figure 3.
TTNT and OS by transplantation status. TTNT (months) in patients with (blue curve) and without +1q (red curve) among those who received chemotherapy alone (A) and those who underwent postinduction transplantation (B). OS in patients with (blue curve) and without +1q (red curve) among those who received chemotherapy alone (C) and those who underwent postinduction transplantation (D).
Figure 4.
Figure 4.
OS by first-line treatment. OS (years) among patients with (blue curve) and without (red curve) +1q among those who received PI- (A), IMiD- (B), and PI plus IMiD–based (C) first-line treatment.
Figure 5.
Figure 5.
Impact of +1q on OS. Comparison of OS (years) in patients with (blue curve) and without +1q (red curve) among those with an HR IgH translocation (A), an SR IgH translocation (B), or trisomy (without IgH translocation) (C). (D) Comparison of OS (years) in patients with +1q without other HR abnormalities (green curve), patients with 1 HR abnormality but without +1q (blue curve), and patients with no +1q or other HR abnormalities (red curve).
Figure 6.
Figure 6.
Impact of 1q copy number on TTNT and OS. Comparison of TTNT (months) (A) and OS (years) (B) in patients with gain of 1 copy of 1q (red curve) and patients with gain of >1 copy of 1q (amplification; blue curve).
See this image and copyright information in PMC

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