Micro-classroom No. 10 Professor Jin Fengyan: Progress in the evaluation of debilitating elderly multiple myeloma

Multiple myeloma (MM) is a malignant disease of abnormal proliferation of cloned plasma cells, which is the second most common malignancy in the blood system in many countries, and is more common in old age and is still incurable

For MM patients, a variety of factors such as age, physical fitness status, cytogenetic abnormalities, and International Staging System (ISS) staging can affect prognosis

Due to the interaction of aging and debilitating, as well as the characteristics of multi-organ and multi-organ involvement, the treatment of MMs in the elderly faces great challenges

To more accurately identify debilitated patients, the International Myeloma Working Group established the IMWG Debilitation Integral System (IMWG-FS)

Figure 1 IMWG attenuated integration system

In addition to IMFS, the revised myeloma comorbidity index (R-MCI), the British Myeloma Research Consortium Risk Prediction Model (MRP), and the Mayo Clinic Frailty Score (Mayo-FI) are also commonly used in clinical debilitation assessment systems (Table 1

Table 1 MM debilitation evaluation system

After determining the patient's physical fitness status through the debilitation assessment system, domestic and foreign guidelines recommend the development of individualized treatment strategies

Regarding the specific treatment plan, the MM diagnosis and treatment guidelines recently issued by the Chinese Anti-Cancer Association (CACA) recommend that patients with good physical fitness choose a standard three-drug combination regimen, of which VRd (bortezomib + lenalidomide + dexamethasone) and Dara-Rd (darrituliumab + lenalidomide + dexamethasone) can be used as the preferred regimen; Patients with average physical fitness can choose a reduced dose of the three-drug combination regimen or a standard two-drug combination regimen; Debilitated patients may choose a reduced combination of two-agent regimen or optimal supportive care (Figure 2)⁴

Figure 2 CACA guidelines recommend treatment for patients with MM with different physical conditions

As MM treatments enter the era of new drugs, existing systems for assessing debilitating are showing increasing limitations
.

In order to further meet the individualized treatment needs of MM patients, a more complete debilitation assessment system
needs to be established.

The ideal system should be as objective and simple as possible in functional assessment; and incorporated MM-specific biomarkers and MM disease signatures; Ability to apply new drugs as well as immunotherapy; The main goal is to improve the patient's PFS and OS, and the secondary goal is to improve the quality of life; And it needs to be validated by forward-looking, multicenter real-world studies
.

But there are still many unanswered questions in the assessment of debilitation in elderly MM patients – how to choose a debilitation assessment tool? How do I explore the Debilitation Assessment Tool? How can individual treatment be tailored in conjunction with dynamic debilitation assessment?

Several recently published studies have explored these questions, including the HOVON 123 study, which explored objective indicators
of weakness.

The study enrolled 240 patients aged ≥ 75 with newly diagnosed MM (NDMM) who assessed muscle mass and function by CT scans, steps, and grip strength on the basis of IMWG-FS, and included the debilitating biomarker P16
.

Preliminary findings suggest that the inclusion of these indicators is more helpful in the identification of debilitated ^patients5
.

In addition, a real-world study conducted by the First Affiliated Hospital of Sun Yat-sen University evaluated the applicability
of the IMWG Geriatric Assessment System (GA) in MM patients in China.

The researchers analyzed eight elderly assessment indicators in 135 MM patients, and confirmed through screening and multivariate analysis that the stand-up-walk timing test (TUG) and nutritional assessment brief (MNA-SF) were independent prognostic factors for ≥-3 AE and OS, and built a more ideal debilitating assessment system based on IMWG ^GA6
.

summary

Assessment of future development directions for debilitation in elderly MM patients:

From defining debilitation to treatment models based on debilitating adjustments

From one-time assessments to dynamic assessments

Whether debilitating based on current treatment is applicable to new immunotherapy

Incorporate measurable, reliable, and reproducible objective biomarkers of weakness (e.
g.
, sarcopenia, inflammatory markers, and markers of aging)

[1] Pawlyn C, et al.
Leukemia.
2020 Feb; 34(2):604-612.

[2] Antonio Palumbo, et al.
Blood.
2015 Mar 26; 125(13):2068-74.

[3] Leukemia (2018) 32:1697–1712.

Chinese Anti-Cancer Association.
Chinese Guidelines for Integrated Diagnosis and Treatment of Tumors (CACA) – Multiple Myeloma.

[5] Sonja Zweegman, et al.
2022 EHA

[6] Juan Li, et al.
2022 EHA P896.

EM-109618Content Approved Date ：9/8/2022

It is for the reference of medical pharmacy professionals only, and reproduction and dissemination are strictly prohibited

Poke "Read the original article" to see more