Risk of Second Primary Cancers in Multiple Myeloma Survivors in German and Swedish Cancer Registries

Chen, Tianhui; Fallah, Mahdi; Brenner, Hermann; Jansen, Lina; Elias, K.; Castro, Felipe A.; Katalinic, Alexander; Emrich, Katharina; Holleczek, Bernd; Geiss, Karla; Eberle, Andrea; Sundquist, Kristina; Hemminki, Kari

doi:10.1038/srep22084

Cited by 17 publications

(19 citation statements)

References 34 publications

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“…Prior studies have shown that the incidence of breast, colon, lung, and prostate cancer may be lower among survivors of myeloma compared with the general population . This was hypothetically ascribed to a decrease in cancer screening after diagnosis of a hematologic cancer .…”

Section: Discussionmentioning

confidence: 99%

“…Prior studies have shown that the incidence of breast, colon, lung, and prostate cancer may be lower among survivors of myeloma compared with the general population. [21][22][23] This was hypothetically ascribed to a decrease in cancer screening after diagnosis of a hematologic cancer. 21,23 Conversely, the nearly 7-fold higher risk of acute leukemia was attributed to the leukemogenic effects of alkylator-based therapy and stem cell transplantation, although the risk of myelodysplasia is notably also increased in patients with monoclonal gammopathy, a premalignant plasma cell dyscrasia.…”

Section: Discussionmentioning

confidence: 99%

“…21,23 Conversely, the nearly 7-fold higher risk of acute leukemia was attributed to the leukemogenic effects of alkylator-based therapy and stem cell transplantation, although the risk of myelodysplasia is notably also increased in patients with monoclonal gammopathy, a premalignant plasma cell dyscrasia. 21,22,24 The introduction of proteasome inhibitors and immunomodulatory drugs, which now are used widely for first-line therapy for myeloma in the United States, 25,26 did not appear to affect the incidence of SPM, although one study suggested that bortezomib treatment may be associated with a lower risk. 10.23 Some clinical trials found an increased rate of SPMs with lenalidomide, yet in a meta-analysis this risk was not observed for patients with common solid tumors.…”

Section: Discussionmentioning

confidence: 99%

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Outcomes of secondary solid tumor malignancies among patients with myeloma: A population‐based study

Barth

Castillo

Olszewski

2018

Cancer

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Background Therapeutic advances have extended survival for patients with myeloma, who may develop secondary cancers. Methods Using the population‐based Surveillance, Epidemiology, and End Results registry (2004‐2015), the authors examined the characteristics, overall and cause‐specific survival, and cumulative incidence function of cancer‐related death among patients with myeloma with secondary cancers of the breast, prostate, lung, colon/rectum, or bladder or melanoma. Each patient was matched based on age, sex, race, and year of diagnosis to 50 controls from a general population who were diagnosed with the index cancer. Results Patients with myeloma with breast, prostate, or lung cancer were more commonly diagnosed at an early stage, whereas the stage distribution did not differ significantly among patients with melanoma, colorectal cancer, or bladder cancer. For all studied cancers except those of the lung, overall mortality was significantly higher among patients with myeloma compared with controls (hazard ratios, 1.84‐2.81). However, the cumulative incidence function of cancer‐related death did not differ (subhazard ratios, 0.84‐0.99) and was surpassed by myeloma‐related deaths (23% to 35% at 5 years). In patients with lung cancer, cancer‐related mortality was uniquely lower among patients with myeloma (subhazard ratio, 0.59; 95% confidence interval, 0.52‐0.68), even after adjustment for stage of disease. There was no significant difference noted with regard to noncancer deaths for any studied solid tumor. Use of surgery (evaluated in patients with nonmetastatic tumors, and in addition matched by disease stage) did not differ between cases and controls, except for fewer prostatectomies being noted among patients with myeloma (odds ratio, 0.56; 95% confidence interval, 0.42‐0.74). Conclusions The results of the current study support curative treatment approaches to secondary cancers among patients with myeloma while highlighting the need for ongoing active myeloma management.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Outcomes of secondary solid tumor malignancies among patients with myeloma: A population‐based study

Barth

Castillo

Olszewski

2018

Cancer

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“…6 Other studies have found MM patients to have an increased risk of developing certain types of second cancers, such as melanoma, nervous system tumors, and kidney and urinary tract tumors, although mechanisms and risk factors are not well understood. [7][8][9][10] Suggested risk factors for second malignancies include treatment-, disease-, environmental-, behavioral-, and host-related factors. 4,[11][12][13] Host-related factors include both genetic and nongenetic; reported nongenetic factors include age, male sex, and obesity.…”

Section: Introductionmentioning

confidence: 99%

The Impact of Prior Malignancies on Second Malignancies and Survival in MM Patients: A Population-Based Study

Jonsdottir

Lund

Björkholm

et al. 2016

Blood

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Background Awareness of second malignancies in patients with multiple myeloma (MM) has been increasing during recent years. We have previously shown that second malignancies are associated with a decreased life expectancy in MM patients. Information regarding prior and second malignancies in MM is limited as these patients are often excluded from clinical trials and previously published results from other groups have been conflicting. In the present study we aimed to evaluate two hypotheses. Firstly we hypothesize that prior malignancy is a proxy for genetic instability that could be a risk factor for subsequent malignancy development in MM patients. There is limited data regarding this association in the literature and in two recent registry studies the results were inconclusive. Secondly, to further assess the clinical implication of prior malignancies in MM patients we assessed survival in these patients compared to MM patients without a history of prior malignancy. Patients and Methods All patients diagnosed with MM from January 1, 1973 to December 31, 2013 were identified from the Swedish Cancer Register. All prior and subsequent malignant diagnoses were identified through cross-linkage within the registry. A Cox regression model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) where prior malignancy was compared in MM patients who developed a subsequent malignancy and MM patients who did not. In another Cox regression model, survival was compared in MM patients with and without a prior malignancy. The same method was used to estimate if there was a dose-dependent relationship, i.e. if an increasing number of prior malignancies was associated with a poorer outcome. Results A total of 22,359 patients were diagnosed with MM during the study period. Of these, 2,620 (12%) patients had one or more prior malignancy diagnosis at the time of MM diagnosis and 1,243 (6%) patients developed subsequent malignancies. Among the MM patients who developed a subsequent malignancy, 148 (12%) had a prior malignancy diagnosis. Hematological malignancies were 7% of prior malignancies and 17% of subsequent malignancies. MM patients with a prior malignancy diagnosis did not have increased risk of developing a subsequent malignancy compared to MM patients without a prior malignancy (HR 1.0, 95% CI 0.9-1.2). MM patients with a prior malignancy diagnosis had a statistically significant 10% increased risk of death (HR=1.1, 95% CI 1.1-1.2, p<0.001) compared to MM patients without a prior malignancy diagnosis. MM patients with 2 or more prior malignancy diagnoses had a 20% increased risk of death (HR=1.2, 95% CI 1.1-1.4, p=0.002) compared to MM patients without a prior malignancy diagnosis (Figure). Summary and Conclusions In our large population-based study we found that prior malignancy negatively impacts survival in MM patients and that more than one prior malignancy decreases survival even further. Interestingly, a prior malignancy did not increase the risk of developing a subsequent malignancy in MM patients. We confirmed prior reports of solid tumors being more common than hematological malignancies, both prior and subsequent to the MM diagnosis. A prior malignancy was associated with a reduced survival in MM patients without being a risk factor for subsequent malignancies. The underlying explanation for this is probably multifactorial, and could include reduced dose intensity of chemotherapy, complications from treatment, or that MM that develops after another malignancy might be biologically different. Given the increase of cancer survivors in general, our findings are of importance both for the individual patients and their families as well as for the treating physician. Figure Survival in MM patients without a prior cancer diagnosis compared to MM patients with one and two or more prior cancer diagnoses Figure. Survival in MM patients without a prior cancer diagnosis compared to MM patients with one and two or more prior cancer diagnoses Disclosures Landgren: Takeda: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees; Medscape: Employment, Other: Chairman for Medscape Myeloma Program; Amgen: Speakers Bureau; Celgene: Speakers Bureau; BMS: Speakers Bureau.

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Section: Introductionmentioning

confidence: 99%

The impact of prior malignancies on second malignancies and survival in MM patients: a population-based study

et al. 2017

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Risk of Second Primary Cancers in Multiple Myeloma Survivors in German and Swedish Cancer Registries

Cited by 17 publications

References 34 publications

Outcomes of secondary solid tumor malignancies among patients with myeloma: A population‐based study

Outcomes of secondary solid tumor malignancies among patients with myeloma: A population‐based study

The Impact of Prior Malignancies on Second Malignancies and Survival in MM Patients: A Population-Based Study

The impact of prior malignancies on second malignancies and survival in MM patients: a population-based study

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