Why carry out this study?
|
Outcomes for patients with diffuse large B cell lymphoma (DLBCL) who relapse or are refractory (R/R) to first-line treatment are poor, especially those who are ineligible for stem cell transplantation (a standard second-line treatment). |
The aim of our clinical systematic literature review was to identify clinical evidence on treatment options for these patients and to assess the feasibility of conducting an indirect treatment comparison (ITC) or network meta-analysis (NMA) to evaluate the relative efficacy and safety of polatuzumab vedotin plus bendamustine-rituximab (pola-BR; a recently approved second-line or later treatment) versus other treatments for R/R DLBCL. |
What was learned from this study?
|
Thirty-seven studies were identified, of which 20 were eligible. Due to a lack of randomized controlled trials (RCTs; seven in total), an ITC/NMA summary of the relative efficacy and safety of the treatment options was not possible, and only two of the seven RCTs had positive outcomes. |
These results highlight the lack of published RCTs to establish the comparative efficacy of treatments for transplant-ineligible R/R DLBCL and the lack of standard of care treatment in this setting. |
Digital Features
Introduction
Methods
Search Strategy
Eligibility Criteria
Study Selection and Data Extraction
Network-Building Analysis
Results
Search Results
Intervention | No. studies | ORR, % | CR % | Median PFS, months | Median OS, months | EFS, % | Median DOR, months | References |
---|---|---|---|---|---|---|---|---|
Axicabtagene ciloleucel | 1 | 82 | 58 | 7.3h | NR | 8.1 | [27] | |
BR | 2 | 46–63 | 15–37 | 3.6–6.7 | NR [30] | 17.3 | ||
GDP | 1a | 63 (vs 55) | 29 (vs 38) | 17.1 (vs 6.0)i | 17.0 (vs 7.0) | 19.6 (vs 11.1)j | [17] | |
Gemcitabine + vinorelbine | 1 | 50 | 14 | 12.9 | [29] | |||
ESHAP | 1b | 62 (vs 60) | 37 (vs 36) | [18] | ||||
Inotuzumab ozogamicin + R | 1c | 41 (vs 44) | 13 (vs 13) | 3.7 (vs 3.5) | 9.5 (vs 9.5) | [20] | ||
Lenalidomide | 4d | 19–28 | 7–12 | 13.6 (vs 7.9) weeks | 7.1 | 10.6 | ||
Lenalidomide + R | 1 | 35 | 35 | NR | 16.5 | [34] | ||
Pixantrone | 1e | 37 (vs 14) | 11 (vs 0) | 5.3 (vs 2.6) | 10.2 (vs 7.6) | |||
Pixantrone + R | 1f | 62 (vs 44) | 36 (vs 22) | 7.3 (vs 6.3) | 13.3 (vs 19.6) | [22] | ||
Pola-BR | 1g | 48.0 (vs 18) | 42.5 (vs 15) | 7.6 (vs 2.0) | 12.4 (vs 4.7) | 31.6 (vs 5.3)k | 10.3 (vs 4.1) | [11] |
R-GemOx | 3 | 44–73 | 34–73 | 5.0–NR | 5.7–11.0 | |||
Tisagenlecleucel | 2 | 50–54 | 40–43 | 2.9–3.2 | 11.1–22.2 | NR |
Baseline Characteristics
Intervention | Reference | Median age (years) | Male sex (%) | Disease severity (%) | Prior lines of therapy (%) | Refractory status (%) | DOR to last therapy |
---|---|---|---|---|---|---|---|
Axicabtagene ciloleucel | [27] | 58 | 67 | IPI 0–2: 52 3 or 4: 48 | ≥ 3: 69 | History of primary refractory disease: 26 Primary refractory at study entry: 2 Refractory to 2L + therapy: 77 | N/A |
BR | [28] | 67 | 42.4 | IPI 0, 1: 33.9 0–2: 35.6 Ann Arbor stage II: 30.5 III: 35.6 IV: 25.4 | 1 prior chemotherapy regimen: 64.4 2: 22.0 Prior rituximab: 96.6 | N/A | N/A |
[32] | 74 | 49 | Ann Arbor stage I–II: 10 III–IV: 89 | 1: 51 2: 21 3: 13 > 3: 15 Prior rituximab: 95 | N/A | N/A | |
GPD | [17]a | 66.2 | 24 | IPI 0, 1: 33 0–2: 69 3: 24 4: 7 | NR | 42 | N/A |
Gemcitabine + vinorelbine | [29] | 65 | 59 | IPI low risk: 41 Low intermediate: 36 High intermediate: 9 High risk: 14 | 1: 64 2: 32 3: 4.5 | N/A | N/A |
ESHAP | [18]a | 51.8 | 28 | IPI intermediate: 16 High: 37 | 1: 43 2: 10 | N/A | N/A |
Inotuzumab ozogamicin + R | 70 | 56 | sIPI 0–1: 16 2: 31 3: 32 4–5: 20 | 1 prior rituximab regimen: 53 2: 35 3: 12 | N/A | N/A | |
Lenalidomide | [9] | 65 | 51 | IPI 0–1: 16.3 2: 44.9 3: 26.5 4–5: 12.2 | 1: 8 2: 16 3: 24 4: 27 ≥ 5: 24 | Refractory to last therapy: 56 Rituximab refractory: 58 Refractory to last chemotherapy: 55 | N/A |
[33] | 66 | 64.5 | IPI low risk: 20.3 Intermediate risk: 62.7 High risk: 17.1 | Median prior regimens: 3 | Refractory to last therapy: 44.2 Rituximab refractory: 53.9 | N/A | |
[24] | 51 | 72 | IPI low risk: 16 Intermediate risk: 68 High risk: 16 | Median prior regimens: 2 | Refractory to last therapy: 72 | N/A | |
[19]a | 69 | 58.8 | NR | 1: 9.8 2: 41.2 ≥ 3: 49.0 ASCT: 25 | N/A | ||
Lenalidomide + R | [34] | 74.2 | 52 | Ann Arbor stage II: 22 III: 26 IV: 52 | Median prior therapies: 3 | N/A | |
Pixantrone | 60 | 66 | IPI 0–1: 30 2: 36 ≥ 3: 34 | Median number of prior chemotherapy regimens: 3 Prior rituximab: 54 Prior stem cell transplant: 16 | Refractory at baseline: 57 | N/A | |
Pixantrone + R | [22] | 73 | 43.6 | IPI 0: 2 1: 13.1 2: 33 ≥ 3: 53.2 Ann Arbor stage I: 6.4 II: 19.9 III: 24.0 IV: 49.7 | 0: 4.8 1: 61.9 2: 21.8 3: 11.58 Prior SCT: 10.6 | N/A | |
Pola-BR | [11]a | 67 | 69.2 | Ann Arbor stage III/IV: 84.6 IPI score 3–5: 53.8 | Median 1: 28.2 2: 35.9 ≥ 3 35.9 Prior anti-CD20 agents: 97.4 | Refractory to last treatment: 74.4 | DOR to last treatment ≤ 12 months: 79.5 |
R-GemOx | [23] | 64 | 67 | Age-adjusted IPI: Low/Low-intermediate: 63 High/intermediate-high: 37 | Median: 2 Prior rituximab: 57 | Primary refractory: 13 | Duration of last remission ≤ 1 year: 20 > 1 year: 67 |
[25] | 69 | 59 | Ann Arbor stage III–IV: 75 Adjusted IPI > 1: 69 | Mean number prior regimens: 1.72 | 59 | N/A | |
[26] | 69 | 55 | Secondary age-adjusted IPI 0–1: 31 2–3: 69 | N/A | Primary refractory: 12 | Duration of last remission ≥ 1 year: 46 < 1 year: 54 | |
Tisagenlecleucel | 56 | N/A | IPI ≥ 2: 73 | 2 Prior lines antineoplastic therapy: 44 3: 31 4–6: 20 Prior ASCT: 49 | 54 | N/A |