Geriatric-guided Care Versus Conventional Care in Elderly Unfit/Frail Patients With Diffuse Large B-cell Lymphoma in First Line Treatment

• Geriatric-guided supportive care (Other): Structured geriatric consultation, along with a nutritional and physiotherapy evaluation, before treatment initiation and with subsequent follow-up assessments aimed at optimizing comorbidity management, nutritional and functional status, along with treatment tolerance.
• Conventional supportive care (Other): Supportive care will be delivered according to local clinical practice

Primary outcomes

• To evaluate whether a geriatric-guided approach improves health-related quality of life (HRQL) in elderly patients with DLBCL eligible for first-line chemoimmunotherapy, compared to a conventional approach. [From the beginning of the study up to 6 months after last enrolled patient (up 30 months from study beginning)]: Change in the Global Health Status/QoL score of the EORTC Quality of Life Core 30 From baseline to end of treatment (6 months after enrollment). EORTC QLQ-C30 questionnaire: ranking from 1 ("not at all") to 4 ("very much").

Secondary outcomes

• To assess changes in the functioning scales and symptom scales of the EORTC QLQ-C30 performed at baseline, 3, 6, and 12 months in both study groups (geriatric-guided vs conventional approach) [From the beginning up to the end of study (up to 36 months)]: Change from baseline in the functioning scales (physical, role, emotional, cognitive, social) and symptom scales (e.g., fatigue, pain, nausea/vomiting) of the EORTC QLQ-C30 at 3, 6, and 12 months. EORTC QLQ-C30 questionnaire: ranking from 1 ("not at all") to 4 ("very much").
• To assess changes in simplified Geriatric Assessment (sGA) performed at baseline, 3, 6, and 12 months in both study groups (geriatric-guided vs conventional approach) [From the beginning up to the end of study (up to 36 months)]: Change in simplified Geriatric Assessment (sGA) classes assessed at baseline, 3, 6, and 12 months. sGA scale: fit, unfit, frail
• To compare eventual dose reductions of therapeutic treatments between groups. [From the beginning of the study up to 6 months after last enrolled patient (up 30 months from study beginning)]: Chemoimmunotherapy dose reductions rate stratified according to therapeutic choices and delivered dose intensity
• To evaluate the prognostic impact of sGA on overall survival (OS) [From the beginning up to the end of study (up to 36 months)]: Overall survival evaluation stratified according to sGA
• To compare the treatment completion rate between groups [From the beginning of the study up to 6 months after last enrolled patient (up 30 months from study beginning)]: Rate of Treatment completion, defined as the proportion of patients who complete the planned chemoimmunotherapy without premature discontinuation.
• To assess early mortality rate (within 90 days) in the two groups. [From the beginning of the study up to 90 days after last enrolled patient (up 27 months from study beginning)]: Early mortality proportion, defined as death from any cause within 90 days of enrollment.
• To compare overall response rate (ORR) and complete response rate (CRR) between groups. [From the beginning of the study up to 6 months after last enrolled patient (up 30 months from study beginning)]: Overall Response Rate (ORR) and Complete Response Rate (CRR), assessed according to Lugano classification at end of treatment,
• To evaluate progression-free survival (PFS) and overall survival (OS) in the two groups. [From the beginning up to the end of study (up to 36 months)]: Progression-Free Survival (PFS) and Overall Survival (OS), defined according to standard criteria, with time measured from date of enrollment.
• To compare hospitalization rates between groups. [From the beginning up to the end of study (up to 36 months)]: Healthcare resource utilization: Incidence of hospital admissions
• To assess caregiver quality of life and caregiver-related outcomes measured by the CareGiver Oncology Quality of life questionnaire (CarGOQoL) at baseline, 3, 6, and 12 months in both groups. [From the beginning up to the end of study (up to 36 months)]: Caregiver-reported outcomes, including caregiver Quality of Life and burden, assessed at baseline, 3, 6, and 12 months using The CareGiver Oncology Quality of life questionnaire (CarGOQoL). CarGOQoL: rank from 0 ("never/not at all") to 5 ("always/enormously")
• To evaluate modifications in the Fried frailty index assessed only in the geriatric-guided arm (performed at baseline, 3, 6, and 12 months) and if there is a concordance between sGA and Fried score. [From the beginning up to the end of study (up to 36 months)]: Change in the Fried frailty index assessed in the geriatric-guided arm, performed at baseline, 3, 6, and 12 months. Assessment if a dynamic change of fitness class is present and if it differs significantly from sGA (performed in both arms). Fried score and sGA: fit (robust), unfit (pre-frail), frail (frail).
• To compare median hospital stay between groups. [From the beginning up to the end of study (up to 36 months)]: Healthcare resource utilization: Mean duration of hospital stay (in days)
• To compare emergency department access rate between groups. [From the beginning up to the end of study (up to 36 months)]: Healthcare resource utilization: Incidence of emergency department accesses
• To compare hospice admission rate between groups. [From the beginning up to the end of study (up to 36 months)]: Healthcare resource utilization: Incidence of patients admitted to hospice during follow-up
• To compare eventual dose delays of therapeutic treatments between groups. [From the beginning of the study up to 6 months after last enrolled patient (up 30 months from study beginning)]: Chemoimmunotherapy dose delays rate stratified according to therapeutic choices and delivered dose intensity
• To evaluate the prognostic impact of Body Mass Index (BMI) on overall survival (OS). [From the beginning up to the end of study (up to 36 months)]: Overall survival evaluation stratified according to BMI value
• To evaluate the prognostic impact of serum albumin on overall survival (OS). [From the beginning up to the end of study (up to 36 months)]: Overall survival evaluation stratified according to serum albumine value
• To evaluate the prognostic impact of caregiver availability on overall survival (OS). [From the beginning up to the end of study (up to 36 months)]: Overall survival evaluation stratified according to caregiver availability

Sex: All, ages: 70 Years to any

Inclusion Criteria:

1. Diagnosis of DLBCL or Follicular Lymphoma (FL) grade IIIB.
2. Age ≥ 70 years.
3. UNFIT or FRAIL status according to sGA evaluated by the onco-hematologist at baseline.
4. Patients eligible to a curative intent standard first line chemoimmunotherapy.
5. Ability to understand and willingness to comply with study procedures.
6. Signature of a written informed consent.

Exclusion Criteria:

1. Patients not meeting at least one of the inclusion criteria listed above.
2. Refuse to sign a written informed consent.

• Benedetta Sordi, MD, Principal investigator, A.O.U. Careggi di Firenze - S.O.D. Ematologia