Клинический консенсус в отношении лечения санитарной трансплантации, недавно диагностировавшийся множественным миэлома: двойной склейка Делфи.

Introduction

Multiple myeloma (MM) is a malignant neoplasm of plasma cells that accounts for 1.8% of all cancers in the USA [ 1 ]. To date, MM remains an incurable disease [ 2 ], primarily affecting the elderly (median age at diagnosis is 69 years, and incidence increases sharply with age), in which the 5-year survival rate (2013–2019) is 60% [ 1 , 3 ].

The treatment landscape for newly diagnosed MM (NDMM) is complex and rapidly evolving, and includes combinations of alkylators, proteasome inhibitors, steroids, anti-CD38 monoclonal antibodies, and immunomodulatory drugs [ 4 ]. While some patients are candidates for stem cell transplantation, others are transplant ineligible (TIE) due to advanced age and/or other underlying diseases or comorbidities [ 4–6 ].

For TIE NDMM, considerations for treatment selection include patient age, fitness, frailty, high-risk cytogenetics, comorbidities, quality of life, and cost/insurance [ 6 , 7 ]. Currently, VRd (bortezomib, lenalidomide, and dexamethasone) and DRd (daratumumab, lenalidomide, and dexamethasone) are the only preferred regimens recommended by the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines ® ) for the primary treatment of nontransplant patients with NDMM with Category 1 evidence [ 8 ]. Other recommended regimens per the NCCN Guidelines include carfilzomib, lenalidomide, and dexamethasone; daratumumab, bortezomib, melphalan, and prednisone; ixazomib, lenalidomide, and dexamethasone; and daratumumab, bortezomib, cyclophosphamide, and dexamethasone [ 8 ]. However, treatments recommended by the NCCN Guidelines as “useful in certain circumstances” are also being prescribed: doublets such as bortezomib and dexamethasone, and Rd (lenalidomide and dexamethasone). Treatments prescribed that are not recommended by the NCCN Guidelines include triplets, such as daratumumab, carfilzomib, and dexamethasone; and quadruplets, such as daratumumab, bortezomib, lenalidomide, and dexamethasone; and daratumumab, carfilzomib, lenalidomide, and dexamethasone [ 9 , 10 ]. Additionally, some clinicians may choose to save more effective triplet and quadruplet treatments for later lines of therapy and to prescribe monotherapy and doublets as first-line (1L) therapy [ 11–13 ].

With the numerous combination treatment options and the heterogeneity of patient variables to consider, there is significant variation in prescribing patterns. The lack of a consistent approach may be associated with a limited body of evidence, as existing clinical trials on TIE NDMM (e.g., SWOG S0777 [ 14 , 15 ], MAIA [ 16–18 ], and ALCYONE [ 19 , 20 ]) lack direct comparisons between the current NCCN Guidelines-preferred treatments, VRd and DRd. Moreover, pivotal trials like SWOG S0777 and MAIA compared triplet therapy with doublet therapy as this was the standard of care at the time of trial design [ 14 , 16 ], and some included therapies (e.g., bortezomib, melphalan, and prednisolone in the ALCYONE trial) more commonly used in countries other than the USA [ 21 , 22 ]. Network meta-analyses have attempted to investigate the overall effectiveness (progression-free survival [PFS] and overall survival [OS]) of various 1L therapies for TIE patients with NDMM, but are limited by potential biases resulting from the variance in patient populations, treatments used, and how data were extracted from each trial [ 9 , 23 , 24 ].

Given the variation in 1L prescribing patterns for TIE patients with NDMM, the lack of head-to-head clinical trials and the scarcity of real-world evidence comparing long-term outcomes and optimal duration of therapy of these regimens, a modified Delphi panel approach was employed to obtain clinical consensus from USA-based physicians on various aspects of 1L treatments to aid physician treatment decision-making.

Methods

Study design

A traditional Delphi technique involves multiple rounds (at least two) of anonymized surveys with controlled feedback at each stage to reduce variation of responses and to move toward consensus. In this study, a modified Delphi panel was conducted between June 2022 and November 2022 to determine the opinions of experts on 1L treatment options for TIE NDMM. This study was not registered on any platform, and there was no piloting of study materials and/or survey instruments. After two rounds of surveys, an online consensus meeting was held via WebEx to allow discussion to reach final consensus where possible or to provide rationale for lack of consensus. A flow diagram of the Delphi process is shown in Figure 1 .

Panel selection

A panel screener was developed using predefined criteria to ensure that the findings of this study are credible, reflective of clinical practice, and generalizable. USA-based and licensed hematologists/oncologists currently managing and treating TIE patients with NDMM in the last 6 months in either an academic or community practice setting were included. Expert panelists had moderate-to-high familiarity with the NCCN Guidelines and were from various geographical locations in the USA to ensure that the results were generalizable to the USA healthcare system. Furthermore, priority was given to panelists who had 50 or more appointments with patients with MM per month and had been in practice for 5–30 years. Priority was given to panelists from sites that had participated in clinical trials in the last 3 years and that had been involved in the development of NCCN Guidelines.

Recruitment of panelists was carried out by a third-party recruiter to ensure both the study sponsor and the study investigators were double-blinded and to avoid compromising the integrity of the study by introducing bias. Anonymity was maintained throughout the modified Delphi process to ensure that initial perspectives were not informed by other survey participants based on their profile/status. Selected panelists were also required to sign an informed consent form, and an honorarium was paid for their participation. During onboarding, panelists were provided with a study brief which included an overview of disease background and the treatment landscape for 1L NDMM, collected through a targeted literature review.

First-round survey

The initial survey of 40 questions was developed based on literature, clinical trials, and key topics that were identified at the commencement of this study. The survey was delivered online as a link via email, which also included detailed instructions on how to complete the survey. The survey consisted of statements regarding the following four areas of focus: 1) prescribing factors impacting 1L therapy, 2) understanding the efficacy of 1L therapy, 3) challenges with 1L therapy, and 4) optimal duration of 1L therapy in TIE NDMM. Panelists were required to answer all questions in the questionnaire and were encouraged to give qualitative feedback. Panelists were also able to provide free-text responses to gather information on their opinions/perceptions on the current regimens available for use as 1L treatment for TIE NDMM. The first-round responses were analyzed to create an anonymized overview of the results and feedback, which was then used to inform development of the second-round survey. Statements that had reached consensus in the first round were summarized and presented to the panel in the second round, but were excluded from the second-round survey.

Second-round survey

The second-round survey was delivered in a similar online format as the first round. The aim of the second round was to understand areas that were nearing consensus and to identify any aspects that required further discussion during the consensus meeting. Panelists were provided with an anonymized overview of the panel's results from the first round for each statement/question as well as their own response. At this time, panelists were given the opportunity to rerate statements from the first round. Furthermore, a new factor that two or more panelists reported in the first round, but that had not been considered previously, was highlighted in the second round and was developed into a new statement to understand whether all panelists considered this to be important. The second-round responses were analyzed, and an anonymized overview of the results was produced to inform the material to be presented to the panel during the consensus meeting.

Determining consensus

Several means for assessing consensus in Delphi studies have been reported; however, there is no agreed best approach [ 25 ]. The definition of consensus for this study was ≥80% of panelists rating their ‘agreement’ between 7 and 9 or ‘disagreement’ between 1 and 3 on a 9-point scale. Furthermore, if ≥80% of panelists reported the same response to an open question provided in the first round, this was considered as reaching consensus and was not carried forward to subsequent rounds.

Consensus meeting

The aim of the meeting was to seek consensus in agreement or disagreement on all remaining statements relating to 1L treatments for TIE NDMM on which consensus had not been reached during the survey rounds. The consensus meeting was conducted online through WebEx and was moderated by the study investigators. Panelists were provided with a brief overview of areas that reached consensus during the survey rounds, but the meeting focused on areas in which there was a lack of agreement. Each statement was presented with the median and range of scores, alongside any rationale provided by the panelists. The panelists were then asked to discuss each statement to evaluate whether consensus could be reached or whether statements needed to be adapted to reach consensus. Panelists were provided an opportunity to update statements throughout the consensus meeting based on the discussion between the panelists and the moderators.

Data analysis

Data from the first and second round of surveys were screened for bias and anomalies before being summarized. To reduce the effects of bias, the median score was calculated for each question, thus preventing single outlying responses from substantially impacting the overall mean value. The number of responses that reached consensus was also recorded. For qualitative responses, thematic analysis was conducted to identify key concepts to be explored in the second round and these were discussed at the consensus meeting.

Results

Delphi panel characteristics

Eighteen expert panelists were recruited and participated in both survey rounds, and nine of them participated in the consensus meeting. Overall, panelists had an average of 19 years of clinical practice experience ( Table 1 ). Thirteen (72%) panelists reported that they typically have more than 50 appointments with patients with MM in a month. Thirteen (72%) panelists considered themselves to be extremely familiar with NCCN Guidelines, with all panelists participating in the development of NCCN Guidelines for MM within the past 5 years. All panelists had participated in MM clinical trials, and 15 (83%) practiced predominantly in an academic setting. Panelists reported that 30% of the patients with MM whom they manage are newly diagnosed, of which, 39% are TIE and 25% are high risk ( Table 1 ).

Summary of consensus statements

As noted earlier, this Delphi panel study intended to obtain expert opinion on the following four areas of focus: 1) prescribing factors for 1L therapy for TIE NDMM, 2) understanding the efficacy of 1L therapy in TIE NDMM, 3) challenges with 1L therapy in TIE NDMM, and 4) optimal duration of 1L therapy for TIE NDMM. An overview of all statements that reached consensus in the survey rounds has been summarized ( Table 2 ) and is discussed in detail below.

Prescribing factors for 1L therapy for TIE NDMM

The prescribing factors were categorized into patient-, disease-, and treatment-related factors. In the first round, consensus in agreement was reached that patient-related factors, such as frailty (89%) and poor Eastern Cooperative Oncology Group performance status (83%), have a strong impact on treatment selection in addition to the treatment-related factors, such as the treatment's effect on PFS and its adverse event (AE) profile (83% for both). Additionally, in the second round, consensus was reached in agreement that the presence of comorbidities (89%) and the treatment's effect on OS (89%) also have a strong impact on the selection of treatment for TIE NDMM ( Table 2 ). The prescribing factors that did not reach consensus, but were discussed during the consensus meeting, are reported in Supplementary Table S1A. Although panelists did not reach consensus on specific comorbidities that impacted their prescribing (Supplementary Table S1A), consensus was almost reached on neuropathy (78%) and chronic kidney disease (67%). Panelists noted that they would opt for a reduced bortezomib dose schedule for patients with neuropathy and that lenalidomide dosing and administration would be modified for patients with chronic kidney disease. Panelists were also close to reaching consensus on older patient age (67%) as a factor that would impact prescribing. Panelists stated that age alone might not necessarily impact the selection of 1L treatment, but older patient age is often associated with comorbidities that would impact treatment selection. With respect to disease-related factors, high-risk cytogenetic profile almost reached consensus (67%), and panelists noted that a patient's prescription may be adjusted based on the type of cytogenetic abnormality; however, they expressed that there are conflicting opinions within the current literature regarding prescription behavior for high-risk patients (Supplementary Table S1A). Further, they noted that even though insurance is not a key deciding factor for treatment selection, they would make modifications to a patient's treatment if insurance coverage for the patient was insufficient or if there was pushback from the insurance provider (Supplementary Table S1A).

Understanding the efficacy of 1L therapy in TIE NDMM

In the first round, consensus was reached that the most efficacious 1L therapy for TIE NDMM is the one that best improves PFS (83%). Additionally, in the second round, consensus in agreement was reached that the most efficacious 1L therapy is also one that best improves OS (83%) and the time to next treatment (TTNT; 89%; Table 2 ). Experts expressed that even though OS is considered the “gold standard” end point in clinical trials, OS is often not available; hence, panelists will prescribe “regimens without having OS reported.” Another “useful barometer” mentioned by panelists was TTNT, as longer TTNT suggests improved effectiveness and safety. The panelists almost reached consensus on minimal residual disease (MRD) negativity (78%) and complete response (CR; 71%) as measures of efficacy (Supplementary Table S1B); however, some panelists thought that these measures are subjectively defined, and a treatment could still be efficacious if it prolongs PFS without achieving MRD negativity or CR.

Consensus was achieved that it is important to use the most efficacious regimen as 1L treatment, either always or in the majority of cases (100%), and fit patients would benefit most from using the most efficacious treatment first (83%). All panelists disagreed with the statement that it is rarely or never important to use the most efficacious regimen as 1L treatment (100%; Table 2 ). When probed on whether all patients would benefit from using the most efficacious treatment first, consensus was not reached. One panelist highlighted that differing schools of thought exist regarding use of the most efficacious therapy for all TIE patients with NDMM, with some clinicians opting for a conservative treatment approach for a fit, standard-risk patient and saving some drugs for later lines versus others advocating for the most effective regimen from the very beginning for all patients (full quote in Supplementary Table S1B).

Sixteen panelists agreed that they consider one regimen to be more efficacious than other regimens. When probed to provide what the expert panelists considered to be the most efficacious treatment, daratumumab-containing treatment was provided in 14 of 16 answers (88%) (DRd [n = 8]; daratumumab, bortezomib, lenalidomide, and dexamethasone [n = 5]; and daratumumab, carfilzomib, lenalidomide, and dexamethasone [n = 1]; Figure 2 ).

Challenges with 1L therapy in TIE NDMM

In the first round, consensus was reached that medication toxicity is a challenge that would prevent the panelists from choosing a drug for frail patients (89%). Consistent with the known toxicity profile, panelists considered neuropathy as the greatest challenge and concern when treating patients with bortezomib (94%) and stated that it has prevented them from considering bortezomib for some patients (89%). In addition, as consistent with the approved labeling, when treating with lenalidomide, the need to modify dosing for patients with renal impairment (94%) was identified as the greatest challenge ( Table 2 ). Nevertheless, panelists noted that some physicians do not consider challenges, such as treatment tolerability or dosing frequency of treatments when prescribing 1L TIE NDMM therapies, as insurmountable (full quote in Supplementary Table S1C).

Optimal duration of 1L treatments in TIE NDMM

In the first round, panelists agreed that treatment-related AEs (94%) and negative impact on a patient's quality of life (89%) are key drivers for discontinuing a drug within a regimen. In the second round, panelists reached consensus that treatment tolerability (94%) and efficacy (89%) are important factors in determining optimal duration of therapy ( Table 2 ). When probed if there was an optimal duration of therapy for the entire 1L regimen for TIE patients with NDMM, half of the panelists agreed while the other half disagreed. It was noted that the observed differences in opinion could have been caused by various interpretations of the term ‘optimal duration’. Some panelists defined optimal duration not as a specific time period but rather as defined per the NCCN Guidelines, which state, “until treatment progression or unacceptable toxicities” (full quote and additional comment in Supplementary Table S1D). Nevertheless, panelists reached consensus that it is important for TIE patients with NDMM to continue with the entire 1L regimen for as long as the benefits of continuous treatment until progression outweigh risks (89%).

When probed regarding discontinuation of treatment for TIE NDMM, panelists agreed that individual drugs from a regimen are discontinued, rather than the entire regimen (89%; Table 2 ). With respect to the two NCCN Guidelines-preferred treatments for TIE NDMM, DRd and VRd, >80% of panelists noted that they have had to discontinue one or more individual drugs in these regimens (83 and 89%, respectively). More specifically, for the VRd regimen, panelists estimated this to occur in a median of 80% of patients, and 13 of 18 panelists (72%) stated that bortezomib is typically the drug to be discontinued first (Supplementary Table S1D). For the DRd regimen, panelists estimated individual drug discontinuation to occur in a median of 53% of patients, and dexamethasone is typically the drug that is discontinued first, per 14 of 18 panelists (78%; Supplementary Table S1D). However, in the consensus meeting, panelists noted that dexamethasone discontinuation is commonly preceded by dose modification.

For other factors that could potentially influence optimal treatment duration—such as treatment duration in clinical trials, patient preference, patient willingness, and MRD negativity—no consensus was reached among the panelists and these factors are included in Supplementary Table S1D.

Overall comments from the expert panel

When panelists were asked if they would choose one NCCN Guidelines-preferred therapy (VRd or DRd) over another, in general, they responded that they preferred DRd as their choice of 1L therapy (full quotes in Supplementary Table S2).

Discussion

The treatment of MM is complex, with numerous patient-related factors to consider, multiple combinations of treatments to choose from, and various sequencing of treatment options available. There is a need for clinical consensus in the prescription of 1L therapy for TIE NDMM to achieve the best long-term outcome and to understand the rationale behind these prescription patterns. Here, we utilized a modified Delphi panel to incorporate the views of 18 MM experts with an average of 19 years in practice on several key aspects relating to 1L therapy for TIE NDMM. Consensus was reached on a total of 27 statements, including five or more statements in each area of interest: prescribing factors relating to patient, disease, and treatment; efficacy of treatments; challenges such as treatment toxicity and dosing; and optimal duration of treatment in 1L therapy for TIE NDMM.

The Delphi panel confirmed that treatment efficacy (e.g., OS, PFS) and toxicity profile were key decision-making factors when prescribing 1L therapy for TIE NDMM. Other important factors to consider when choosing therapy were patient frailty, poor Eastern Cooperative Oncology Group performance status, and presence of comorbidities. These statements align with the current literature that patient comorbidities and frailty should be considered along with treatment efficacy [ 26 , 27 ]. Even though age, treatment preference, and insurance coverage of the patients were important factors to consider, panelists did not reach consensus on these factors as having a strong impact on selection of 1L therapy for TIE NDMM. Of all the statements probed under prescribing factors, the panel did not reach consensus on any as having ‘no impact’, demonstrating that prescribing treatment involves balancing the best treatment options available with various patient-, disease-, and treatment-related factors.

Despite the introduction of newer therapies that offer better PFS and OS, there is ongoing debate about the philosophies of controlling versus curing MM, in which some physicians may opt to use the least toxic regimens first and reserve more aggressive therapies for later [ 13 ]. More recently, there are evolving schools of thought that the most effective treatment should be prescribed early for all patients to provide the best opportunity for durable disease control and improved survival [ 11 , 12 ]. Results from our Delphi panel confirmed that all expert panelists agreed that it was important to use the most efficacious treatment either always or in the majority of cases, and 83% of panelists agreed that fit patients would benefit most from using the most efficacious regimens first. It was agreed that the most efficacious 1L therapies for TIE NDMM were regarded as treatments that improve OS, PFS, and TTNT of the patient. The panelists almost reached consensus regarding the importance of MRD and CR, which could be due to the current acceptability of these measures as end points in clinical trials [ 28 , 29 ] and, therefore, they are considered when determining a regimen's effectiveness. MRD and CR have been associated with longer PFS and OS [ 30–32 ], and the use of MRD negativity to aid in patient prognosis and to inform treatment decision is on the rise [ 31–33 ]. However, a lack of standardization of MRD assessment techniques poses a problem in the interpretation of data and comparison of clinical trials [ 34 ]; this is also reflected by the fact that the US FDA and the EMA have published guidelines on the use of MRD in clinical trials, but neither supports the use of MRD as a surrogate for efficacy [ 29 ].

Panelists agreed that they consider one regimen to be more efficacious than others, and most of the regimens that were suggested (14 of 16) as being more efficacious were daratumumab-containing triplets or quadruplets. This was further reinforced when panelists stated in the consensus meeting that they preferred DRd as 1L therapy compared with VRd due to better tolerability and overall efficacy. A similar finding was recently reported by Lonial et al. [ 35 ], in which after evaluating efficacy and safety data from published clinical trials, a panel of experts considered DRd to be the preferred 1L treatment regimen for most TIE patients with NDMM. The difference between the Lonial study and the Delphi panel approach described in this article is that the Delphi panel was double-blinded, which enabled the panelists to express their independent opinions regarding prescribing factors that affect the selection of 1L treatment for TIE patients with NDMM, challenges with the treatments currently used in routine clinical practice, and the optimal duration of treatment. Given the double-blinded nature of this study, panelists' responses would reflect their own clinical preference based on their years of clinical practice, in addition to the efficacy and safety data from the published clinical trials and treatment guidelines, without bias from the majority of the panelists. Recent data comparing MAIA (DRd vs Rd) and SWOG S0777 (VRd vs Rd) trials using Rd-anchored indirect comparison (after propensity score reweighting) showed a hazard ratio of 0.60 (95% CI: 0.39–0.90) favoring DRd over VRd [ 36 ]. A previous study comparing PFS in TIE patients with NDMM from the MAIA trial (DRd vs Rd) and the Flatiron Health database (VRd vs Rd; bortezomib and dexamethasone vs Rd) using Rd as the common anchor showed that patients treated with DRd had significantly lowered risk of progression or death compared with those treated with VRd (hazard ratio: 0.68; 95% CI: 0.48–0.98) [ 37 ]. Furthermore, through the use of modeling and simulation, a recent publication showed that using DRd as 1L therapy resulted in longer median OS compared with saving it as second-line therapy after VRd or Rd [ 12 ].

AEs were considered as one of the challenges when prescribing current 1L treatments for TIE NDMM. Consistent with the known safety profile, panelists agreed that neuropathy is the greatest challenge when treating patients with bortezomib, and it has prevented them from prescribing bortezomib. This is in line with the findings in the SWOG S0777 trial in which a quarter of patients had to stop VRd treatment prematurely due to neuropathy related to bortezomib [ 14 , 15 ]. Panelists also agreed that modification of lenalidomide dosing for patients with renal impairment per the approved labeling is challenging. Panelists did not reach consensus on many statements regarding challenges in 1L TIE NDMM therapy on topics of treatment tolerability, dosing frequency, and patient requirement to travel for treatment. However, panelists noted that these proposed challenges for 1L therapies were considered limitations but did not prevent them from prescribing these therapies as 1L treatment in TIE NDMM.

Finally, panelists largely agreed that treatment should be continued until progression as long as the benefits outweigh the risks; this is in line with the literature [ 38 ]. Most statements that were agreed upon by the panelists to influence optimal duration of 1L therapy were related to treatment tolerability, efficacy, and patients' quality of life. Results also highlighted that when discontinuing treatment for TIE patients with NDMM, individual drugs rather than the entire regimen were usually discontinued. However, the individual drug that was discontinued first was different for the two Category 1 NCCN Guidelines-preferred triplet regimens: bortezomib for VRd and dexamethasone for DRd. As noted in Lonial et al., experts recommended against the extended use of corticosteroids with daratumumab for the sole purpose of preventing infusion-related reactions given the low rate of these reactions reported with the subcutaneous formulation of daratumumab [ 35 ]. In addition, as demonstrated in Manier et al., the dexamethasone-sparing regimen (DR vs Rd) provided a favorable safety profile in frail patients yet still achieved deep and rapid responses [ 39 ].

This study used a well-established and reliable Delphi panel approach to attain clinical consensus in 1L treatment of TIE NDMM, for which limited data are available on the comparative assessment of preferred treatments (DRd vs VRd). While clinical trials in TIE patients with NDMM are available, direct head-to-head comparisons of preferred treatments are lacking, and indirect treatment comparisons have limitations. This study was able to obtain the expert opinions of 18 USA-based hematologists/oncologists with an average of 19 years of experience in treating patients with MM. As this study examines key factors and understandings of 1L TIE NDMM treatment that are not drug- or regimen-specific, it provides valuable insights that can inform decision-making about existing and future therapies in the USA.

This study is particularly insightful due to the strengths of its methodology. The Delphi panel is a well-established approach that uses systematic and controlled feedback through which consensus is achieved in a way that fits the research question with a high level of accuracy. Additionally, due to the double-blinded nature of this study, panelists were able to express their independent opinions during the group process without fear of repercussion or judgment from group opinion and without the bias caused by the effect of dominant individuals in group dynamics. The Delphi panel method utilizes anonymous responses; thus, each voice is weighted equally in such a study and lengthy discussions are avoided. Furthermore, this study considers clinician preference, challenges with 1L therapies, and optimal duration of 1L therapy based on the panelists' years of clinical practice that cannot be achieved through an indirect treatment comparison.

This study is subject to some limitations. First, only a subset (n = 9) of the total number of panelists (n = 18) were available during the final consensus meeting. Although the target was to include a smaller number of panelists in the consensus meeting than the survey rounds to facilitate discussion and gain more insight on 1L treatment topics, fewer panelists may mean that not all expert opinions included in the first two rounds of surveys were fully represented in the consensus meeting. Second, topics such as transplant eligibility were not explicitly defined to the panelists before the start of the study. Expert panelists were expected to respond to the surveys based on their everyday practice and considerations for transplant eligibility. The results from this Delphi panel represent the views of the expert panelists at the time of the study; however, owing to the rapid advancement in the development of MM therapies, these views may evolve as more clinical and real-world data become available.

Conclusion

A Delphi panel of USA-based clinicians, who are experts at managing and treating TIE NDMM, agreed that it is important to use the most efficacious treatment upfront as 1L therapy for TIE NDMM in most cases. Daratumumab-containing regimens (triplet and quadruplet) were considered the most efficacious by nearly all panelists. In addition, the panelists agreed that treatment should be continued until progression as long as the benefits outweigh the risks. This study contributes to the understanding of 1L treatment options for TIE NDMM and may aid in the decision-making process for physicians when there is a lack of head-to-head clinical trials and real-world evidence among the preferred treatment options for 1L TIE NDMM.

Supplementary Material

Supplementary Table S1 and S2

Funding Statement

This work was supported by Janssen Scientific Affairs, LLC.

Supplemental material

Supplemental data for this article can be accessed at https://doi.org/10.1080/14796694.2024.2342228

Author contributions

R Fonseca, A Rossi, and FE Davies conceived the idea and designed the research. R Medhekar, J Voelker, T Homan, J Wilcock, A Karakusevic, J Cochrane, D Bridge, R Perry, and S Kaila carried out data collection and analysis. All authors discussed the results, provided input, and reviewed the final manuscript.

Financial disclosure

This work was supported by Janssen Scientific Affairs, LLC. J Wilcock, A Karakusevic, J Cochrane, D Bridge, and R Perry have no conflicts of interest to report. R Medhekar: Janssen employee and/or shareholder. J Voelker: Janssen employee and/or shareholder. T Homan: Janssen employee and/or shareholder. S Kaila: Janssen employee and/or shareholder. A Rossi, Adaptive Biotechnologies: scientific advisory board; BMS: scientific advisory board; GSK: scientific advisory board; Janssen: scientific advisory board; Sanofi: scientific advisory board. FE Davies, AbbVie: scientific advisory board; Amgen: scientific advisory board; BMS Celgene: scientific advisory board; GSK: scientific advisory board; Janssen: consultancy, scientific advisory board; Oncopeptides: scientific advisory board; Regeneron: scientific advisory board; Sanofi: consultancy, scientific advisory board; Takeda: scientific advisory board. R Fonseca, AbbVie: consultancy; Adaptive Biotechnologies: consultancy; Amgen: consultancy; Antengene: board of directors; AstraZeneca: consultancy; Binding Site: consultancy; BMS Celgene: consultancy; Caris Life Sciences: scientific advisory board; Janssen: consultancy; Merck: consultancy; Takeda: consultancy; Pfizer: consultancy; Pharmacyclics: consultancy; RA Capital: consultancy; Regeneron: consultancy; Sanofi: consultancy; other: patent for fluorescence in situ hybridization in multiple myeloma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

Medical writing and editorial support were provided by J Lin of Eloquent Scientific Solutions, and funded by Janssen Scientific Affairs, LLC.

Ethical conduct of research

This research was funded by Janssen Scientific Affairs, LLC. Recruitment of panelists was carried out by a third-party recruiter to ensure both the study sponsor and the study investigators were double-blinded and to avoid compromising the integrity of the study by introducing bias. Anonymity was maintained throughout the modified Delphi process to ensure that initial perspectives were not informed by other survey participants based on their profile/status. Selected panelists were also required to sign an informed consent form, and an honorarium was paid for their participation. The use of anonymized quotes in this publication was granted by the panelists. Ethical approval was not required as the work was focused on literature and data review, as well as experts opinion. No participants were used, interviewed, or contacted for any of the research goals.

Previous presentations

The data in this manuscript were previously presented in part as an online abstract at the European Hematology Association 2023 Hybrid Congress, Frankfurt, Germany, and as a poster at the 20th International Myeloma Society Annual Meeting and Exposition, Athens, Greece [ 40 , 41 ].

References

Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Associated Data

Supplementary Materials

Supplementary Table S1 and S2