Appendix: Multiple Myeloma Treatment Options for Newly Diagnosed, Relapsed, and Refractory Disease

2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Kimberly Noonan, MS, RN, ANP, AOCN ◽  
Teresa S. Miceli, RN, BSN, OCN ◽  
Patricia Mangan, RN, MSN, APRN-BC ◽  
Sandra Rome, RN, MN, AOCN, CNS
Keyword(s):  
Multiple Myeloma ◽  
Treatment Options ◽  
Refractory Disease ◽  
Newly Diagnosed

COMPARISON OF FRAILTY SCORES IN NEWLY DIAGNOSED PATIENTS WITH MULTIPLE MYELOMA: A REVIEW

2019 ◽  
pp. 1-7 ◽  
Author(s):  
H. Mian ◽  
M. Brouwers ◽  
C.T. Kouroukis ◽  
T.M. Wildes
Keyword(s):  
Multiple Myeloma ◽  
Older Patients ◽  
Treatment Options ◽  
Clinical Settings ◽  
Newly Diagnosed ◽  
Future Directions ◽  
Malignant Plasma Cell ◽  
Co Morbidity ◽  
Morbidity Index ◽  
Frailty Score

Multiple myeloma is a malignant plasma cell disease, which typically affects older patients, with a median age at diagnosis of 70 years. The challenge in treating older patients is to accurately identify ‘fit’ patients that can tolerate more intensive treatment to maximize disease control, while simultaneously identifying vulnerable or ‘frail’ patients who may develop toxicity with significant morbidity and mortality, requiring different treatment options or dose modification. Multiple frailty scores have been devised for multiple myeloma over the years in newly-diagnosed patients. This paper gives an overview of the three common frailty measurements: the International Myeloma Working Group Frailty Score, Mayo Clinic Frailty Score and the Revised Myeloma Co-Morbidity Index. We will summarize the derivation, validation, usability and applicability of these scores in different clinical settings, emphasizing the main strengths and limitations for each index score. We will also highlight future directions in the operationalization of frailty in multiple myeloma.

scholarly journals Undertreatment of Older Patients with Newly-Diagnosed Multiple Myeloma: Real World Evidence from a Canadian Registry Cohort

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 268-268 ◽  
Author(s):  
Hira S Mian ◽  
C. Tom Kouroukis ◽  
Gregory R Pond ◽  
Hsien Seow ◽  
Jonathan Sussman
Keyword(s):  
Older Adults ◽  
Multiple Myeloma ◽  
Real World ◽  
Older Patients ◽  
Treatment Options ◽  
Newly Diagnosed ◽  
Drug Usage ◽  
Novel Drugs ◽  
One Year ◽  
Novel Drug

Introduction Multiple myeloma (MM) is a malignant plasma cell disease and is considered a disease of older patients as the median age at diagnosis is 70 years. In recent years, the overall survival of patients with MM has improved due to the increasing number of treatment options and better supportive care. However, older patients (age >65) have not benefitted equally from the same gains. There is a paucity of information regarding clinical outcomes in this age cohort given that older patients are often under-represented in clinical trials and prospective studies. Real-world data may allows us to examine the trends in practice patterns over time and help us understand disparities in treatment options and overall patient outcomes in older patients with MM at a population level. Methods We conducted a retrospective population-based study using administrative data from the Institute of Clinical Evaluative Sciences (ICES), which maintains a central database of health records for all patients in the publicly funded health care system for the province of Ontario, Canada. All patients with newly-diagnosed multiple myeloma, identified using the ICD-O-3 code 9732/3 (Multiple Myeloma) between the years 2007-2017, were included to form the cohort. Autologous transplant within one year of diagnosis was captured in the database using a combination of physician billing codes and hospital procedure/discharge codes. Novel drugs usage for transplant ineligible patients was defined as the receipt of thalidomide, lenalidomide and bortezomib in any combination within one year of diagnosis. No treatment was defined as patients that did not receive a transplant, novel drugs or non-novel drugs (melphalan and cyclophosphamide) within one year following diagnosis. Results A total of 11,875 patients with newly-diagnosed myeloma were identified between the years 2007-2017. The proportion of newly-diagnosed MM patients who were older (age >65 years) increased from 60% of those diagnosed in 2007 to 68% of those diagnosed in 2017. The rates of autologous transplantation in older patients with MM increased from 4 to 10%. Overall those who underwent transplant had improved outcomes with decreasing one-year mortality from nearly 24% in 2007 down to 3% in 2017. Novel drugs were increasingly being used in older patients that were transplant ineligible with up to 42% receiving it within one year of diagnosis in 2017. In transplant ineligible older adults using novel drugs, one- year mortality ranged from 15% to 24%. The rates of older adults with newly-diagnosed MM not treated within one year of diagnosis was on average 49% although that number marginally declined from 54% in 2007 to 47% in 2017. Among those that did not receive treatment, 48% of individuals on average (range 40-57%) were not alive at one-year following diagnosis. Conclusion Our results demonstrate that although gains are being made in older adults with newly-diagnosed MM with increasing rates of transplantation and novel-drug usage over the last decade, there remains a sizeable cohort of older patients that do not receive any treatment within one year of diagnosis. While a limitation of our study may be the inclusion of some smouldering cases of myeloma, the mortality for older patients not treated continues to remain high with approximately half the patients not alive at one year following diagnosis. This study represents one of the largest cohort studies done to date over a decade demonstrating the ongoing low rates of no treatment and high rates of one-year mortality for older patients with MM. Further identification of factors associated with no treatment, transplantation and novel drug usage in older patients with MM are currently being explored. Table. Disclosures Mian: Amgen: Consultancy; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Pond:Roche Canada: Employment, Other: Stock; Takeda (DSMC membership): Other: Honorarium.

scholarly journals HLC Pair Suppression as a Risk Factor for Bacterial Bloodstream Infections and Early Mortality in Newly Diagnosed Intact Immunoglobulin Multiple Myeloma Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Jose Luis Garcia de Veas Silva ◽  
Maria Trinidad Gonzalez Cejudo ◽  
Alberto Garcia Perojil Jimenez ◽  
Maria del Señor Garcia Lopez Velez ◽  
Rafael Garcia Rios Tamayo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Immune System ◽  
Treatment Options ◽  
Bloodstream Infections ◽  
Early Death ◽  
High Sensitivity ◽  
Underlying Disease ◽  
Newly Diagnosed ◽  
Life Threatening ◽  
The Impact

Despite the outstanding progresses in Multiple Myeloma treatment options in the last decades, it remains an incurable disease nowadays. Infectious events are a complication due to an impaired immune system associated with MM, sometimes a life-threatening one, particularly on the first months after the diagnosis. Both the underlying disease and treatment can contribute to the infection risk, so a biomarker that assess this risk could be highly relevant for a more tailored management of the patient. The measurement of the heavy+light chain (HLC) pairs of immunoglobulins in serum allows the quantification of both the monoclonal component and the non-monoclonal immunoglobulin of the same isotype. This approach has demonstrated high sensitivity for the detection of the clonality and prognostic value for MM. HLC pair suppression itself has prognostic power and it has been proposed to be a reflection of the immune system’ attempt to control the tumor. In this study we evaluated the impact of the HLC pair suppression on the rate of bloodstream infections (BSI) and early death in 115 newly diagnosed MM patients. Twenty-one percent of the patients suffered a BSI in the first 6 months after diagnosis, of which 58% died within this period, accounting to 67% of the early deaths in global and highlighting the major impact of infections on MM patients in a “real world” setting. Severe HLC pair suppression identified patients with a higher risk of early BSI (HR: 6,97, p=0,009), and extreme HLC pair suppression together with BSI event and age >65 were independent risk factors for early death (p<0,001). Based on these factors, a stratification model was generated to allow identify patients at a higher risk of early death and poorer OS, with an apparently better performance than the ISS on the early death context. In conclusion, HLC pair suppression associates with both a higher risk of life-threatening early infection and early death in newly diagnosed MM patients. Patients older than 65 with extreme HLC pair suppression and BSI are at a high risk of early death, and thus patients presenting with these criteria have a very adverse prognosis.

Improving Survival in Multiple Myeloma: Impact of Novel Therapies.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3594-3594 ◽  
Author(s):  
Shaji Kumar ◽  
S. Vincent Rajkumar ◽  
Angela Dispenzieri ◽  
Martha Q. Lacy ◽  
Suzanne R. Hayman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Median Time ◽  
Treatment Options ◽  
Entire Group ◽  
High Dose ◽  
Novel Therapies ◽  
Newly Diagnosed ◽  
The Past ◽  
Improvement In Survival

Abstract Background: Recent advances in the therapy of multiple myeloma (MM) have greatly increased the treatment options for this uniformly fatal plasma cell malignancy. It is not clear if introduction of novel therapies and the increased use of high dose therapy (HDT) in the past decade have translated into better outcome for patients (pts) with MM. Methods: We examined the outcome of two cohorts of pts seen at our institution. The first cohort consisted of 387 pts who relapsed after HDT and was examined for potential improvement in survival following relapse after HDT. These pts were divided into two groups; those who relapsed before or after December 31, 2000. The second cohort consisted of 2981 patients with newly diagnosed MM seen between January 1971 and December 2006 and was used to examine the trends in overall survival (OS). Results: Among those relapsing after HDT, there were 245 males (63%); median (range) age at HDT was 57 years (32.8–75.4) and the median time to HDT was 8.1 months (1–90 months) from diagnosis. The median time to relapse was 13.2 months (1.1 months-10.3 years) from HDT. In this cohort, a clear improvement in OS from time of relapse was seen over the past decade, with those relapsing after 2000 having a median OS of 23.9 months (95% CI; 19.8, 27.6) compared to 11.8 months (95% CI; 8.7, 14.9) for the rest (P < 0.001) (Figure 1). In a multivariate analysis, the effect of the date of relapse on survival was independent of other prognostic factors such as relapse <12 months after HDT, abnormal cytogenetics, and B2M > 5.5 mg/dL. Pts who were treated with one or more of the newer drugs (thalidomide, lenalidomide, bortezomib) had longer survival from relapse (30.9 months (95% CI; 23.6, 38.2) compared to 14.8 months (95% CI; 11.3, 18.4); P < 0.001) for others. Among the newly diagnosed MM cohort, the median age at diagnosis was 66 years (20.2 – 97 years), and 1,770 (59.4%) were males. The median follow up for the entire group was 27.4 months (0–29.4 years); and at the time of analysis 558 patients (18.7%) were alive with a median follow up of 32.7 months (0–29.4 years). Pts diagnosed in the last decade had an improved OS (44.8 months) compared to those diagnosed before this period (29.9 months; P < 0.001) (Figure 2). The improvement in survival seen in the last decade among newly diagnosed patients was predominantly among those younger than 65 years (60.3 mos vs. 33.3 mos improvement in median survival); compared to those over 65 at diagnosis (26.5 mos vs. 32 mos). Conclusion: In this study, for the first time, we demonstrate definite proof for improved outcome in patients with myeloma, both in the relapsed setting as well as at diagnosis, a change that is likely to continue with increased use of these drugs. Figure Figure Figure Figure

How should we treat newly diagnosed multiple myeloma patients?

Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 488-495 ◽  
Author(s):  
María-Victoria Mateos ◽  
Jesús F. San Miguel
Keyword(s):  
Quality Of Life ◽  
Multiple Myeloma ◽  
Elderly Patients ◽  
Alkylating Agents ◽  
Treatment Options ◽  
Prolonged Treatment ◽  
Term Therapy ◽  
Close Monitoring ◽  
Newly Diagnosed

AbstractMultiple myeloma (MM) is the second most frequent hematological disease. Two-thirds of newly diagnosed MM patients are more than 65 years of age. Elsewhere in this issue, McCarthy et al discuss the treatment of transplantation candidates; this chapter focuses on the data available concerning therapy for non-transplantation-eligible MM patients. Treatment goals for these non-transplantation-eligible patients should be to prolong survival by achieving the best possible response while ensuring quality of life. Until recently, treatment options were limited to alkylators, but new up-front treatment combinations based on novel agents (proteasome inhibitors and immunomodulatory drugs) plus alkylating agents have significantly improved outcomes. Other nonalkylator induction regimens are also available and provide a novel backbone that may be combined with novel second- and third-generation drugs. Phase 3 data indicate that maintenance therapy or prolonged treatment in elderly patients also improves the quality and duration of clinical responses, extending time to progression and progression-free survival; however, the optimal scheme, appropriate doses, and duration of long-term therapy have not yet been fully determined. The potential for novel treatment regimens to improve the adverse prognosis associated with high-risk cytogenetic profiles also requires further research. In summary, although we have probably doubled the survival of elderly patients, this group requires close monitoring and individualized, dose-modified regimens to improve tolerability and treatment efficacy while maintaining their quality of life.

scholarly journals Management of multiple myeloma in the newly diagnosed patient

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 498-507 ◽  
Author(s):  
María-Victoria Mateos ◽  
Jesús F. San Miguel
Keyword(s):  
Multiple Myeloma ◽  
Elderly Patients ◽  
Hematopoietic Cell Transplantation ◽  
Treatment Options ◽  
Young Patients ◽  
New Drugs ◽  
Novel Agents ◽  
Term Therapy ◽  
High Dose ◽  
Newly Diagnosed

AbstractMultiple myeloma is the second most frequent hematological disease. The introduction of melphalan as high-dose therapy followed by autologous hematopoietic cell transplantation (HDT/ASCT) for young patients and the availability of novel agents for young and elderly patients with multiple myeloma have dramatically changed the perspective of treatment. However, further research is necessary if we want definitively to cure the disease. Treatment goals for transplant-eligible and non–transplant-eligible patients should be to prolong survival by achieving the best possible response while ensuring quality of life. For young patients, HDT-ASCT is a standard of care for treatment, and its efficacy has been enhanced and challenged by the new drugs. For elderly patients, treatment options were once limited to alkylators, but new upfront treatment combinations based on novel agents (proteasome inhibitors and immunomodulatory drugs) combined or not with alkylators have significantly improved outcomes. Extended treatment of young and elderly patients improves the quality and duration of clinical responses; however, the optimal scheme, appropriate doses, and duration of long-term therapy have not yet been fully determined. This review summarizes progress in the treatment of patients with newly diagnosed multiple myeloma, addressing critical questions such as the optimal induction, early vs late ASCT, consolidation and/or maintenance for young patients, and how we can choose the best treatment option for non–transplant-eligible patients.

scholarly journals Autologous Hematopoietic Stem Cell Transplantation Overcomes Primary Refractory Disease in Multiple Myeloma Patients Treated with Novel Agents

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1996-1996
Author(s):  
Gunjan L Shah ◽  
Meier Hsu ◽  
Sean Devlin ◽  
David J Chung ◽  
Hani Hassoun ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Research Funding ◽  
Refractory Disease ◽  
Newly Diagnosed ◽  
Hematopoietic Stem ◽  
Novel Agent

Abstract Introduction: Autologous hematopoietic stem cell transplantation (Auto HSCT) has been shown to prolong progression free (PFS) and overall survival (OS) in patients with multiple myeloma (MM), with the depth of response pre-transplant previously correlated with PFS, but not OS. Even in patients receiving proteasome inhibition and immunomodulatory agents as induction, up to 25% of newly diagnosed patients achieve less than a partial response (PR). We aimed to evaluate outcomes after Auto HSCT for patients with primary refractory MM. Methods: Between 1/2009 and 12/2012, we identified 95 newly diagnosed symptomatic MM patients treated at our institution with novel agent induction regimens and upfront Auto HSCT. Based on IMWG criteria, patients were separated into those achieving >= PR (CR, VGPR, PR) and those who are primary refractory (PrRef) as defined by stable or progressive disease (SD/PD) to first line therapy. Characteristics were compared by the Fisher's Exact test. PFS and OS were calculated in a landmark analysis from transplant and estimated by Kaplan-Meier methods and compared by the log rank test. Results: Sixteen patients (17%) had PrRef disease, with a median age of 53 vs 59 yrs in those who achieved >=PR (p=0.04). Demographic and clinical characteristics were otherwise not statistically different between the two groups: 56 vs 65% were male; 69 vs 80% Caucasian; 69 vs 48% had ISS Stage I disease with 19 vs 14% having high risk cytogenetics; 81 vs 84% had lytic lesions; and 31 vs 51% had extramedullary disease at diagnosis in PrRef pts vs >PR pts, respectively. All patients received induction regimens including either bortezomib (44 vs 38%), lenalidomide (31 vs 24%), or both (25 vs 37%) (p=0.68). Compared with 32% of >=PR pts, 94% of the PrRef pts were treated with additional therapy prior to Auto HSCT (p<0.001), with 5/15 achieving VGPR, 6/15 PR, and 4/15 SD/PD prior to Auto HSCT. Tandem Auto HSCT was performed in two PrRef vs one >= PR patient. Response to Auto HSCT was a 38 vs 58%, 25 vs 25%, 38 vs 14%, and 0 vs 4% for CR, VGPR, PR, and SD/PD, in PrRef vs responding pts respectively (p=0.19). Maintenance therapy, primarily with lenalidomide, was given to 69 vs 78% (p=0.52). Median PFS from transplant was 41 months (95% CI 16 - not reached ) in PrRef pts compared to 53 months, (95%CI: 31 - not reached) in >=PR pts (p=0.51). With a median follow-up of 36.5 months (range 9.5-63 months) in surviving patients, median OS from transplant was not reached in either group (p=0.77)(Figures 1 and 2). For the PrRef pts, 3-yr OS from transplant was 77% (95%CI 43-92%) compared to 87% (95%CI 77-93%) in >=PR pts. Conclusion: A small portion of MM patients have primary refractory disease after induction therapy with bortezomib and lenalidomide. Demographic and disease characteristics, other than age, were not able to differentiate these patients. However, Auto HSCT was an effective therapy regardless of response to novel agent based induction therapy. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Hassoun: Celgene: Research Funding; Novartis: Consultancy; Takeda: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees. Lesokhin:Efranat: Consultancy; Aduro: Consultancy; Janssen: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Genentech: Research Funding. Landgren:BMJ Publishing: Honoraria; BMJ Publishing: Consultancy; Onyx: Research Funding; International Myeloma Foundation: Research Funding; Onyx: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria; Medscape: Honoraria; Celgene: Consultancy; Bristol-Myers Squibb: Consultancy; Medscape: Consultancy; Onyx: Consultancy. Landau:Onyx: Honoraria, Research Funding; Spectrum Pharmaceuticals: Honoraria; Takeda: Research Funding; Prothena: Consultancy, Honoraria; Janssen: Consultancy; Janssen: Consultancy. Giralt:SANOFI: Consultancy, Honoraria, Research Funding; CELGENE: Consultancy, Honoraria, Research Funding; AMGEN: Consultancy, Research Funding; JAZZ: Consultancy, Honoraria, Research Funding, Speakers Bureau; TAKEDA: Consultancy, Honoraria, Research Funding.

scholarly journals Clinical Characteristics and Outcomes of AML Patients Treated with Frontline CPX 351 or HMA/Venetoclax: A Single Institution's Experience

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1252-1252
Author(s):  
Aleksander L. Chojecki ◽  
Justin Arnall ◽  
Danielle Boselli ◽  
Kristyn Y. DiSogra ◽  
Allison Karabinos ◽  
...  
Keyword(s):  
Research Funding ◽  
Clinical Characteristics ◽  
Treatment Options ◽  
Standard Of Care ◽  
Response Rates ◽  
Similar Response ◽  
Refractory Disease ◽  
Newly Diagnosed ◽  
Frontline Treatment ◽  
To Receive

Abstract Introduction: Treatment options for newly diagnosed patients (pts) with acute myeloid leukemia (AML) have historically been limited. The combination of a hypomethylating agent and venetoclax (HMA/Ven) has emerged as standard of care treatment for elderly and/or unfit pts with newly diagnosed AML. Liposomal cytarabine/daunorubicin (CPX-351) has also become standard of care therapy for pts with AML with myelodysplasia related changes or therapy-related AML. Despite being an intensive regimen, CPX-351 may have a more favorable toxicity profile compared to other intensive regimens. As a result, CPX-351 may be offered to older fit pts who may not have been candidates for traditional induction regimens. As the landscape for frontline treatment options evolves, there are now overlapping pt populations who may be eligible for either frontline treatment option. A retrospective study that included clinical trial pts demonstrated similar response rates in pts treated with HMA/Ven and CPX-351 (Asghari Blood 2019). Similarly, a study of secondary AML pts receiving HMA/Ven and CPX-351 showed no difference in remission rate or survival (Salhotra Am J Hematol 2021). There remains a shortage of data describing clinical characteristics of pts selected for and treated with standard-of-care HMA/Ven and CPX-351. We present a study on our center's experience. Methods: The purpose of this study was to evaluate the clinical characteristics and outcomes of adult pts with newly diagnosed AML who were treated with either CPX-351 or HMA/Ven as initial therapy. Consecutive pts treated with either of these two induction therapies between August 2017 and June 2021 were evaluated retrospectively. Pts were eligible for response evaluation if they received at least 3 doses of CPX-351 or 28 days (1 cycle) of venetoclax ("response cohort"). All pts treated with CPX-351 or HMA/Ven were included in survival analysis ("survival cohort"). Response assessment is based on ELN-2017 criteria. Pt characteristics were described and compared using Fisher's Exact tests. Kaplan-Meier methods were used to summarize overall survival, and log-rank tests were used for the comparison of frontline therapies. Cox proportional-hazards regression estimated hazard ratio (HR), 95% confidence interval (CI), and interactions between frontline therapy and age at induction start. Results : A total of 79 pts were identified receiving frontline HMA/Ven or CPX-351; 61 pts (77%) were evaluable for response. Of the response cohort, 21 (34%) were treated with CPX-351 and 40 (66%) with HMA/Ven; pt characteristics are described in Table 1. CPX-351 pts were younger at start of induction (P&lt;0.001); many pts in both treatment groups had unfavorable ELN risk scores at diagnosis (CPX 43%, HMA/Ven 41%; P&gt;0.99). 33% and 23% of the HMA/Ven cohort achieved CR and CRi respectively; in the CPX-351 cohort 57% and 5% achieved CR and CRi respectively. A greater fraction of CPX-351 pts proceeded to allogeneic stem cell transplant than HMA/Ven pts (67% vs 23%; P&lt;0.001). No differences were detected in achievement of MRD negativity by flow cytometry (P=0.51) or molecular profile (P=0.52). Median follow-up for all pts was 18.9 months; 42 deaths occurred. Differences in survival between the frontline therapies were not detected in the survival cohort (HR, 1.31; 95% CI, 0.67 to 2.57; P=0.43) nor the response cohort (HR, 0.97; 95% CI, 0.45 to 2.09; P=0.93); these results were unaffected by adjustments for age at induction, ELN risk score, and transplant status. 8 pts who initially received CPX-351 and had refractory disease later went on to receive HMA/Ven reinduction; 2 achieved CRi, 2 MLFS, 3 Refractory and 1 Death in Aplasia. 1 pt who initially received HMA/Ven with refractory disease went on to receive CPX-351. This pt was refractory to CPX-351. Conclusion: HMA/Ven and CPX-351 are effective frontline treatment options with similar response rates and survival outcomes in newly diagnosed adults with AML. Pts treated with CPX-351 were younger and more likely to proceed with allogeneic transplantation, in line with standard practice. Though there was heterogeneity in pt populations, age did not appear to affect outcomes. As the landscape for standard-of-care upfront treatment for AML continues to evolve, further studies are warranted to determine optimal therapy selection and sequencing. Figure 1 Figure 1. Disclosures Arnall: Novo Nordisk: Speakers Bureau. Symanowski: Carsgen: Consultancy; Immatics: Consultancy, Other: DSMB Member; Eli Lilly: Consultancy, Other: DSMB Member. Avalos: JUNO: Membership on an entity's Board of Directors or advisory committees. Copelan: Amgen: Consultancy. Grunwald: Cardinal Health: Consultancy; Daiichi Sankyo: Consultancy; Astellas: Consultancy; Agios: Consultancy; Janssen: Research Funding; PRIME: Other; Karius: Consultancy; Bristol Myers Squibb: Consultancy; AbbVie: Consultancy; Pfizer: Consultancy; Blueprint Medicines: Consultancy; Gilead: Consultancy; Incyte: Consultancy, Research Funding; Amgen: Consultancy; Med Learning Group: Other; Sierra Oncology: Consultancy; MDEdge: Other; PER: Other; Trovagene: Consultancy; Stemline: Consultancy.

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