【2022 ASH Field Frontier】Treatment status and stratified prognosis of multiple myeloma

The 64th Annual Meeting of American Hematology (ASH) will be held in person and online on December 10~13, 2022, this article selects the relevant abstracts announced at the conference on the treatment status of multiple myeloma, the prognosis stratification of special populations, etc.
, for details, and see below!

Status of treatment

Poster #2111

Worldwide Network for Blood and Marrow Transplantation (WBMT) Global Study on Baseline Characteristics and Clinical Outcomes in NEWLY Diagnosed Multiple Myeloma Patients Undergoing Upfront Autologous STEM Cell Transplantation, a Study Off 61,725 Patients from 629 Centers

Key author: Laurent Garderet

Key message: This study is the largest study to date to be analysed for outcomes after ASCT worldwide
.
The most common pretreatment regimen is melphalan
at 200 mg/^m2.
Globally, non-relapse mortality at 12 months is as low as 1%, while recurrence is 16%.

The median OS was 7 years and the median PFS was 3 years
.
ASCT remains an effective and safe treatment option
for patients with NDMM.

Poster #2260

Real-World Treatment Patterns and Outcomes of Patients with Newly Diagnosed Multiple Myeloma: An Analysis Using National Health Insurance Service Database

Key author: Yoosun Lee

Key information: The study included a total of 8367 patients, of whom 2442 received transplants and 5925 did not; The median OS for the overall population was 3.
36 years, and the median OS of transplanted patients was significantly better than that of patients who did not receive transplant (7.
04 years versus 2.
32 years).

Although treatment regimens containing new drugs have improved OS, ASCT remains an important treatment for
prolonging OS.

Poster # 1894

Efficacy of Frontline Treatments for Newly Diagnosed Transplant-Ineligible Multiple Myeloma, a Network Meta-Analysis

Key author: Maggie Wong

Key information: A network meta-analysis comparing the effectiveness of different first-line regimens in patients with TIE NDMM showed that daratumumab-containing multidrug regimens were the preferred treatment
for patients with TIE NDMM, regardless of cytogenetic risk.

Poster #3194

A Retrospective Comparison of the Side Effect Prevalence and Severity of Multiple Myeloma Triplet vs Quadruplet Induction Therapy

Key author by Nathan W.
Sweeney

Key information: A total of 1204 patients were included in the study, and overall, the four-drug combination regimen for multiple myeloma did not increase the incidence of serious adverse reactions compared with the three-drug combination regimen; Therefore, the choice of drug regimen needs to pay more attention to treatment interruption due to adverse reactions than the number of drugs in the regimen, so as to obtain continuous disease control
.

Poster #1900

Cause Specific Analysis of Very Early and Early Mortality in Patients with Multiple Myeloma: Continued Improvements and Changes over Last 25 Years

Key author: Vinit Singh

Key message: Early mortality from multiple myeloma has declined in recent years, but remains a significant clinical challenge
.
Non-MM-related causes have been increasing as a proportion of early mortality compared to MM-related causes
.
Early implementation of cause-specific responses, such as lifestyle changes, early screening, and infection prevention, can further reduce early mortality
in high-risk populations.

Poster #2266

Multiple Myeloma Transplant: Examining the Intersection of Access, Age and Race

Key author by Ashley E.
Rosko

Key information: Socioeconomic status at the age, ethnic, and regional levels affects transplant acceptance and overall survival after MM diagnosis
.
Socioeconomic status (SES) at the regional level may be an important driver of MM survival independent of transplantation
.

Hazard stratification

Poster #3229

Is the Second Revision of the International Staging System (R2-ISS) for Multiple Myeloma Valid in a Real-World Population from China?

Key author: Wenqiang Yan

Key message: The R2-ISS scoring model can effectively predict the prognosis
of MM patients in the real world.
Although 1q21+ leads to adverse outcomes, different copy numbers do not produce additional adverse effects, providing strong evidence
for the revision of 1q21+ in R2-ISS.

Oral #648

Combining Plasma Cell Leukemia-like Status with the Second Revision of the International Staging System Improves Risk Classification

Key author by Davine Hofste op Bruinink

Key message: Plasmacytic leukemia-like status (PCL gene transcription signature) has independent prognostic value in the R2-ISS classification of NDMMs.

Plasma cell leukemia-like MM with R2-ISS IV may result in an abnormally high risk of NDMM, with a median OS of only 7 months
.

Poster #1906

The Impact of Dynamic Assessment of Risk Stratification at the Time of Disease Progression in Patients with Multiple Myeloma

Key Author: Huishou Fan

Key message: Risk stratification reassessment
can be performed using ISS and R-ISS at the time of disease progression.
The prognostic significance of restaging at progression is greater than the prognostic value of staging at diagnosis, and patients with higher stages have a worse prognosis
.

Poster #1901

A Simple Risk-Scoring Model for Estimating the Prognostic Impact of 1q Gain in Patients with Newly-Diagnosed Multiple Myeloma

Key author: Fengyan Jin

Key message: The heterogeneity of patients with +1q MM results in very variable prognostic outcomes
.
The study proposes a simple three-tier risk scoring model to guide such HRMM patients to better manage disease risk
.

Poster #4518

The Independent Adverse Prognostic Significance of 1q21 Gain/Amplification in Newly Diagnosed Multiple Myeloma Patients

Key author: Hongying You

Key information: Clinically significant end-stage organ damage and high tumor burden in 1q21+ patients are independent high-risk cytogenetic factors for poor prognosis in patients with NDMM, where 4 or more copy numbers and major clone locations are significantly associated
with prognosis.
The combined analysis of FISH, CytoScan and related chromosomal abnormalities can more accurately analyze clinical features, efficacy assessment, and prognosis, identify patients with poor prognosis early, and increase the likelihood of
future treatment strategies based on risk stratification.

Poster #1892

Evolving Pattern Improves the IMWG 2/20/20 Classification for Patients with Smoldering Multiple Myeloma

Key author: Luis Gerardo Rodríguez-Lobato

Key message: To add a dynamic surveillance model of disease progression to the IMWG classification of SMM patients (evolving-2/20/20 system), when the baseline M protein ≥ 30 g/L or <30 g/L, the number of M protein increases by at least 10% or 25%, respectively, in the first 12 months after diagnosis, defined as disease progression
.
The model enables more precise risk stratification
for very high-risk patients.
These patients require more intensive follow-up and may require early treatment
.

Oral #646

Individualized Treatment-Adjusted Risk Stratification in Newly Diagnosed Multiple Myeloma

Key author: Francesco Maura

Key Message: This study describes the first individualized predictive model for NDMM patients, which incorporates data from 1840 patients undergoing various treatments to analyze the interaction of genomic, clinical, and therapeutic factors to enable personalized risk prediction and treatment decisions for NDMM
.

Oral #647

Increased Levels of Circulating Plasma Cells in Patients with Newly Diagnosed Multiple Myeloma Are Independently Associated with Poor Prognosis

Key author: Evangelos Terpos

Key message: The results confirm that increased levels of circulating tumor cells (CTCs) in NDMM have a negative and independent prognostic effect and suggest that this factor can be used to improve models
of risk stratification.
Because liquid biopsy is more representative of the entire tumor burden than tissue biopsy, CTC levels can serve as a new marker
for real-time assessment of a patient's disease and immune status.

Poster #4528

Evaluating Concordance between International Myeloma Working Group (IMWG) and Simplified Frailty Index (SFI) Among Older Adults with Multiple Myeloma (MM)

Key author: Andrew Gahagan

Key information: Frail patients accounted for 25% (IMWG-FI) to 32% (SFI) of older MM patients, suggesting only modest agreement between SFI and IMWG FI assessment systems, and even worse
when patient-reported versions of ECOG PS were used.
Therefore, potential misclassification
should be taken into account when comparing the results of the two debilitating indices.

Oral #171

Need for Dynamic Frailty Risk Assessment Among Older Adults with Multiple Myeloma: A Population-Based Cohort Study

Key author: Hira S Mian

Key message: Weakness improves or worsens over time, so current frailty can be a better predictor of treatment outcomes
than baseline status.
Future strategies aim to further evaluate and incorporate dynamic frailty monitoring to provide more targeted treatment
.

Prognostic parameters

Oral #251

Stem Cell Autograft Minimal Residual Disease Negativity Improves Outcomes after Autotransplant for Multiple Myeloma

Key author: Noriko Nishimura

Key information: PFS and OS improved in patients with MRD-negative autologous stem cell grafts after ASCT treatment, so the potential utility of MRD status of autologous stem cell grafts as a prognostic parameter for clinical outcomes is important for guiding post-ASCT therapy
.

Poster #2288

Prognostic Value of Translocation 11; 14 in Patients with Relapsed/Refractory Myeloma Receiving Anti-CD38 Therapy

Key author by Ghulam Rehman Mohyuddin

Key information: In this real-world study, after treatment with CD38 monoclonal antibody, there were t(11; 14) Patients with mutations with no t (11; 14) No significant difference
in survival outcomes was observed compared to patients with mutations.
More and more t(11; 14) Patients receiving BCL2 inhibitors such as veneclaclaxla, however, CD38 monoclonal antibody treatment is still an important part of the treatment regimen of such patients, and the synergistic strategy of combining bcl-2 inhibitors and CD38 monoclonal antibody should be further explored
in clinical trials.

Oral #644

Co-Occurrence of High-Risk Lesions Is a Consistent Predictor of Ultra-High Risk Multiple Myeloma in Newly Diagnosed and Relapsed/Refractory Patients – Meta-Analysis of 5,808 Trial Patients

Key author: Martin F.
Kaiser

Key message: This large meta-analysis demonstrates for the first time consistent risk identification
by extended genograms in NDMM and RRMM.
Our results strongly support the evaluation and reporting of single-hit/high-risk and double-hit/ultra-high-risk patient populations in clinical trials.

These data also highlight the importance of obtaining an extended gene profile in routine patient care, with the minimum requirement being to obtain gain(1q), t(4; 14) and del (17p) full results
.

Oral #115

Impact of Presence and Amount of Clonal Plasma Cells in Autografts Affect Outcomes in High-Risk Multiple Myeloma Patients Undergoing Autologous Hematopoietic Stem Cell Transplant

Key author: Oren Pasvolsky

Key message: Clonal plasma cells (CPCs) in autografts have important implications
for prognosis after ASCT in patients with high-risk multiple myeloma.
Even in patients with above-VGPR and MRD-negative CR prior to ASCT, the presence and number of CPCs were highly predictive factors
of low PFS and OS.

Poster #3222

Impact of High-Risk Disease on Outcome after CAR-T Cell Therapy for Multiple Myeloma: A Meta-Analysis of 759 Patients

Key author: Nico Gagelmann

Key message: High-risk cytogenetics is significantly associated
with poor prognosis after receiving CAR-T therapy for RRMM.
Although there was no significant difference in ORR in EMD, the risk of recurrence and poor survival was significantly increased
in these patients.

Oral #762

Risk-Adapted Therapy Directed According to Response (RADAR, UK-MRA Myeloma XV) – Comparing MRD-Guided Treatment Escalation and De-Escalation Strategies in Patients with Newly Diagnosed Myeloma Suitable for Stem Cell Transplantation

Key author: Kwee Yong

Key information: The UK-MRA RADAR study is a national, multicentre, risk-adapted, multi-arm multi-phase phase II/III trial
that guides TE NDMM treatment based on disease response.
The genetic risk classification and the patient's MRD status determine whether ASCT increases or decreases the intensity
of treatment.

Poster #4490

English: The Co-Occurrence of 1q21+/1q23+ and t(4; 14) Abnormalities with Specific Clone Size Is Predictive of Shorter Response to Transplant in Patients with Multiple Myeloma

Key author: Michael P.
Ozga

Key information: The study showed that MM patients with single-chromosomal abnormalities were associated with combineds of 1q21+/1q23+ and t(4; 14) Differences
in high-risk patients.
The effect of quantitative clones on survival prognosis showed that patients with fewer clones were 20% higher than patients with fewer clones [1q21+ (or 1q23+)> and t(4; 14) >30%] patients had better survival outcomes
.
Therefore, clinicians should pay attention not only to the presence of high-risk chromosomal abnormalities, but also to the number of abnormal clones that also affect the survival prognosis and disease characteristics
of patients.

Poster #3202

Analysis of Clinical Characteristics and High-Risk Factors of Patients with Extramedullary Relapse Multiple Myeloma

Key author: XiaoYan Yue

Key information: In patients treated with bortezomib-based regimens, the extramedullary recurrence rate is approximately 24%.

Extraosseous (EME) recurrence is more common and survival is extremely low
.
Elevated LDH, hypercalcaemia, extramedullary involvement, and splenomegaly at diagnosis are independent risk factors
for extramedullary recurrence in patients with NDMM.

Poster #3178

Plasma Cell Leukemia: A Multicenter Retrospective Study of 130 Patients

Key author by Iloabueke Chineke

Key information: This multicenter retrospective study shows the actual clinical treatment pattern and survival prognosis of PCL patients in the United States in the era of new drugs, and the survival analysis results emphasize that sPCL has a poor prognosis and the urgent need for new treatment options, and transplantation can prolong the overall survival
of pPCL and sPCL patients under limited statistics.

Poster #4539

Predictors of Response to Radiation Therapy and of Progression to Multiple Myeloma in Patients with Solitary Bone and Extramedullary Plasmacytomas

Key author by Beatrice Fregonese

Key information: Radiotherapy has a local control effect on isolated bone-associated plasmacytoma (SBP) and isolated extramedullary plasmacytoma (EMP), although progression to MM remains a serious problem, with SBP more likely to progress to MM (64% of patients progressing to MM at 5 years and 28% of EMP).

Oral #469

Circulating Clonal Plasma Cells at Diagnosis and Peripheral Blood Measurable Residual Disease Assessment Provide Powerful Prognostication Biomarkers in Newly-Diagnosed Multiple Myeloma Patients Treated without Autologous Transplant

Key author: Prashant Ramesh Tembhare

Key Information: This prospective study suggests that circulating clonal plasma cell quantification at diagnosis provides a strong prognostic factor for NDMM patients who have not been treated with autologous transplantation, and that MRD assessment of peripheral blood provides an independent biomarker for predicting event-free survival and OS
.

Poster #2321

Real-World Study of Patients with Triple-Class Exposed Relapsed or Refractory Multiple Myeloma: Analysis across a Spectrum of Advanced Disease Stage Patients in the United States

Key author: Qiufei Ma

Key message: Although the number of patients with MM with triple exposure, triple refractory, and quintally exposed is increasing, there is no good standard treatment regimen
.
Under current treatments, the short duration of treatment, the number of outpatient visits, the number of hospitalizations and the number of days, and the cost of treatment are high, these data highlight the huge unmet
demand for new treatment options for such patients.

Poster #3204

Patient Characteristics and Survival Outcomes of Lenalidomide Exposed non- Refractory vs.
Lenalidomide Refractory Multiple Myeloma Patients in the HONEUR Federated Data Network

Key author: Roman Hajek

Key message: Patients with Len-refractory MM had significantly shorter
overall survival compared to patients exposed to Len but not refractory MM.
Therefore, there is a great need
for effective treatment options to prolong survival outcomes in people refractory to Len.

Poster #4530

Drug Class Refractoriness, Not Number of Prior Lines of Therapy (LOT), Properly Classify Patients with Relapsed and Refractory Multiple Myeloma (RRMM) Receiving Contemporary Regimens

Key author: Luciano J.
Megala Costa

Key information: In patients treated with RRMM, resistance to the drug species, rather than the number of lines of prior treatment, is an important factor
influencing ORR and PFS.

Poster #2283

Impact of Disease Progression, Line of Therapy, and Response on Health-Related Quality of Life in Multiple Myeloma: A Systematic Literature Review

Key author: Rafael Fonseca

Key message: Improvement in HRQoL is strongly associated
with desirable treatment outcomes such as delayed disease progression, fewer treatment lines, and deeper remissions.
However, heterogeneity in study design and the limited number of available studies on HRQoL and disease progression, treatment regimens, and treatment response suggest that further targeted studies are needed in this area to improve patient outcomes
.

Poster #4536

Update on the Outcome of M-Protein Screening Program of Multiple Myeloma in China: A 7-Year Cohort Study

Key author: Wenjing Wang

Key message: Routine M protein screening in hospitalized patients leads to earlier diagnosis and better patient outcomes
.
This study updates the results
of 7 years of follow-up for MM patients diagnosed by screening-driven and end-organ symptom-driven models.