Effect of t (11;14) Abnormality on Outcomes of Patients With Newly Diagnosed Multiple Myeloma in the Connect MM Registry

Gasparetto, Cristina; Jagannath, Sundar; Rifkin, Robert M.; Durie, Brian G.M.; Narang, Mohit; Terebelo, Howard R.; Toomey, Kathleen; Hardin, James W.; Wagner, Lynne I.; Ailawadhi, Sikander; Omel, James; Srinivasan, Shankar; Dhalla, Mazaher; Catamero, Donna; Kitali, Amani; Agarwal, Amit; Abonour, Rafat

doi:10.1016/j.clml.2021.08.007

Cited by 13 publications

(17 citation statements)

References 28 publications

(29 reference statements)

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“…In this retrospective study of 591 NDMM patients diagnosed over two decades, we found a prevalence of t(11;14) (17.6%), consistent with other studies (5,6,8,10,18,20,22,27,30,32). We also noted that this group of patients represents a subgroup of MM with unique biological and clinical characteristics, with outcomes similar to those of the SR group (except ISS-1 patients) but bene ting less from the introduction of novel agents in rst line in terms of response and PFS.…”

Section: Discussionsupporting

confidence: 91%

“…In the present study, we focused on one of these MM subtypes: the t (11;14). Some studies have attempted to analyze the prognostic signi cance of t (11;14) in terms of response and survival (5,8,24,25,32), but, to the best of our knowledge, this is the rst to explore the value of t(11;14) as a predictor of response to new drugs or chemotherapy-containing regimens in rst line as well as the prognostic value in the era of novel agents, in a representative and unique series, because almost half of the patients received chemoschemes and the others received novel agents.…”

Section: Discussionmentioning

confidence: 99%

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Multiple myeloma and t(11;14): prognostic significance and impact of novel agents on response and survival.

Puertas

González‐Calle

Sobejano

et al. 2022

Preprint

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Multiple myeloma (MM) patients with t(11;14) present unique biological features and their prognosis is not well established. We report a retrospective study of 591 MM patients, 17.6% of whom had t(11;14). It was designed to determine the prognostic impact of this abnormality and the effect of novel agents on the response and outcomes. Three groups were established based on their cytogenetics: 1) t(11;14); 2) high-risk chromosomal abnormalities; and 3) standard risk (SR). After 80.1 months (1.2-273.8 months) of follow-up, no differences were observed in overall survival (OS) between the t(11;14) and SR groups (75.8 vs. 87.2 months; P = 0.438). However, in ISS-1 stage patients, MM t(11;14) individuals had shorter OS than those in the SR group (62.9 vs. 126.7 months; P = 0.004). Treatment of MM t(11;14) with novel agents did not improve their overall response rate (ORR) or complete response (CR) compared with those who received conventional therapy (ORR: 87.2% vs. 79.5%, P = 0.336; CR: 23.4% vs. 12.8%, P = 0.215). This effect translated into similar PFS (39.6 vs. 30.0 months; P = 0.450) and OS (107.6 vs. 75.7 months; P = 0.175). In summary, MM t(11;14) patients did not benefit from the introduction of novel agents as much as SR patients did, indicating that other therapies are needed if their outcome is to be improved.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Multiple myeloma and t(11;14): prognostic significance and impact of novel agents on response and survival.

Puertas

González‐Calle

Sobejano

et al. 2022

Preprint

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“…In summary, our study indicates that, while the cytogenetic underpinnings of AL amyloidosis are generally similar across racial groups, IgH translocations are potentially more prevalent among AAs with AL amyloidosis—similar to prior observations in multiple myeloma [ 3 – 6 ]. Although this correlation may be mediated by ancestry, it is important to acknowledge that patient-identified racial categories are social constructs, which rely on a combination of skin color, geographic location, culture and religion.…”

supporting

confidence: 86%

“…In multiple myeloma, younger age at disease onset among AAs and clustering of cases within families suggested an underlying genetic predisposition according to ancestry [ 2 ]. Efforts to characterize biological determinants of racial disparities in multiple myeloma revealed differences in cytogenetic architecture, with translocations t(11;14), t(14;16), and t(14;20) occurring more frequently and deletion 13q14 less frequently among individuals of African ancestry [ 3 – 6 ]. In one study, t(11;14) was found to be associated with shorter survival in AAs—a marked contrast to its neutral risk in the general multiple myeloma population [ 6 ].…”

mentioning

confidence: 99%

Differences in the cytogenetic underpinnings of AL amyloidosis among African Americans and Caucasian Americans

et al. 2022

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“…The t (11;14) (q13;32) translocation [t (11;14)] is found in about 20% of patients with MM, but studies examining its prognostic ability is different, and data on outcomes from first-line therapy are lacking ( 11 ). The resent study from retrospective reviews have shown that t (11;14) is associated with intermediate outcomes in patients treated with novel agents, as compared with patients who have standard- or high-risk cytogenetic aberrations ( 12 ).…”

Section: Discussionmentioning

confidence: 99%

Palbociclib regulates the expression of dihydrofolate reductase and the cell cycle to inhibit t (11;14) multiple myeloma

Wang¹,

Wang²,

Wang³

2022

Ann Transl Med

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Background Multiple myeloma (MM) with t (11;14) has a unique biology. New combinations of novel agents are needed to improve the prognosis of patients with t (11;14) MM. As a selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), palbociclib (PAL) has been used to treat various malignancies, including breast cancer, ovarian cancer, and so on. However, the effects of PAL on MM remain unclear, and thus, further investigations are warranted. Methods Two t (11;14) MM cell lines, U266 and KMS27, were used in this study. The cell viability and cell cycle were detected to evaluate the anti-myeloma effect of the combination of pralatrexate (PTX) and methotrexate (MTX) with PAL. Three-dimensional (3D) spheroid and mouse models were built to verify the effect of the combination treatment. Western blot was used to detect the expressions of Minichromosome Maintenance Complex Component 2 (MCM2), Minichromosome Maintenance Complex Component 3 (MCM3), and dihydrofolate reductase (DHFR). Results It was observed that PAL had obvious anticancer effects on U266 and KMS27 cells, which had synergistic effects together with PTX and MTX. Importantly, it was found that PAL could promote cell cycle genes including MCM2 and MCM3, and increase the number of MM cells in the G1 phase. Moreover, PAL reduced the expression level of DHFR and exerted its anticancer effects on MM cells by targeting DHFR. It was also determined that PAL exerted anticancer effects on MM in the spheroid and mouse models. Conclusions PAL exerted obvious anticancer effects on t (11;14) MM cells, which had synergistic effects together with PTX and MTX. PAL could promote cell cycle genes and the G1 phase of MM cells. Moreover, PAL reduced the expression level of DHFR and exerted its anticancer effects on t (11;14) MM cells by targeting DHFR.

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Effect of t (11;14) Abnormality on Outcomes of Patients With Newly Diagnosed Multiple Myeloma in the Connect MM Registry

Cited by 13 publications

References 28 publications

Multiple myeloma and t(11;14): prognostic significance and impact of novel agents on response and survival.

Multiple myeloma and t(11;14): prognostic significance and impact of novel agents on response and survival.

Differences in the cytogenetic underpinnings of AL amyloidosis among African Americans and Caucasian Americans

Palbociclib regulates the expression of dihydrofolate reductase and the cell cycle to inhibit t (11;14) multiple myeloma

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