All content on this site is intended for healthcare professionals only. By acknowledging this message and accessing the information on this website you are confirming that you are a Healthcare Professional. If you are a patient or carer, please visit the Lymphoma Coalition.
Introducing
Now you can personalise
your Lymphoma Hub experience!
Bookmark content to read later
Select your specific areas of interest
View content recommended for you
Find out moreThe Lymphoma Hub website uses a third-party service provided by Google that dynamically translates web content. Translations are machine generated, so may not be an exact or complete translation, and the Lymphoma Hub cannot guarantee the accuracy of translated content. The Lymphoma Hub and its employees will not be liable for any direct, indirect, or consequential damages (even if foreseeable) resulting from use of the Google Translate feature. For further support with Google Translate, visit Google Translate Help.
The Lymphoma & CLL Hub is an independent medical education platform, sponsored by Beigene and Roche, and supported through educational grants from Bristol Myers Squibb, Ipsen Biopharmaceuticals, Pfizer, and Pharmacyclics LLC, an AbbVie Company and Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC View funders.
Bookmark this article
While approximately 60% of patients with diffuse large B-cell lymphoma (DLBCL) respond to frontline chemoimmunotherapy, the prognosis for patients who relapse after first line (and subsequent) therapy is poor, highlighting an unmet need for patients with relapsed or refractory (R/R) DLBCL. The single-arm, phase II LOTIS-2 study investigated the antibody-drug conjugate loncastuximab tesirine in patients with R/R DLBCL following ≥2 systemic treatment regimens, including patients with high-risk disease types, and found antitumor activity and an acceptable safety profile in this patient population. Spira, et al.1 recently published a study in Clinical Lymphoma Myeloma and Leukemia that analyzed the effect of loncastuximab tesirine on health-related quality of life (HRQoL), symptoms, and tolerability in patients with R/R DLBCL enrolled in LOTIS-2 (NCT03589469). Here we summarize the key findings.
The LOTIS-2 study was a multicenter, single-arm, open-label phase II trial that enrolled 145 patients aged ≥18 years (Table 1). Patients received loncastuximab tesirine as a 30-minute intravenous infusion on Day 1 of each 3 week treatment cycle at a dose of 150 μg/kg for two cycles and then 75 μg/kg for subsequent cycles.
Patient-reported outcomes were measured using the EQ-5D-5L and the Functional Assessment of Cancer Treatment–Lymphoma (FACT-Lym) instruments at baseline, Day 1 of each treatment cycle, and at the end-of-treatment visit.
The EQ-5D-5L is a self-assessed quality-of-life questionnaire. The scale measures quality of life on five dimensions including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each level is rated on the five-component scale that describes the degree of problems in that area (i.e. I have no problems walking about, slight problems, moderate problems, severe problems, or unable to walk). This tool also has the EQ visual analog scale (EQ VAS) which measures overall health, with a score of 100 representing “the best health you can imagine” and a score of 0 representing “the worst health you can imagine.”2
The FACT-Lym questionnaire is used to assess aspects of health-related quality of life for patients with lymphoma. It contains a generic core questionnaire called the Functional Assessment of Cancer Therapy–General (FACT-G) which is a compilation of 27 items to assess components including physical well-being, social/family well-being, emotional well-being, and functional well-being. The FACT-Lym also contains an additional 15 items specifically for evaluating response to treatment in patients with non-Hodgkin lymphoma called the Lymphoma Subscale (Lym S).3
Table 1. Patient characteristics*
Patient characteristics, % (unless otherwise stated) |
N = 145 |
---|---|
Histologies |
|
DLBCL (not otherwise specified) |
87.6 |
High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements |
7.6 |
Primary mediastinal large B-cell lymphoma |
4.8 |
Disease stage |
|
Transformed disease |
20 |
Double-hit or triple-hit disease |
10.3 |
Advanced disease (stage IV) |
64.1 |
Advanced disease (stage III) |
13.1 |
Male |
59 |
White |
90 |
Age |
|
Median age, years |
66 |
≥65 years |
55 |
≥75 years |
14 |
Prior treatment |
|
Median† |
3 |
Stem cell transplant |
16.6 |
CAR T-cell therapy |
9 |
BCL, B-cell lymphoma; CAR-T, chimeric antigen receptor; DLBCL, diffuse large B cell lymphoma. |
Table 2. Results from mixed models for EQ VAS and FACT-Lym change scores*
MID prespecified threshold (range) |
Change from baseline to C2D1 |
Change from baseline to C9D1 |
Change per cycle (slope) |
||||
---|---|---|---|---|---|---|---|
Est. (95% CI) |
p value |
Est. (95% CI) |
p value |
Est. (95% CI) |
p value |
||
EQ VAS |
7 |
0.42 (−2.20 to 3.04) |
0.749 |
5.00 (1.75–8.25) |
0.003 |
0.65 (0.26–1.04) |
0.001 |
FACT-Lym physical well-being |
2.5 (2–3) |
−0.24 (−0.95 to 0.46) |
0.494 |
−0.03 (−0.93 to 0.86) |
0.941 |
0.03 (−0.08 to 0.14) |
0.606 |
FACT-Lym social/family well-being |
— |
−0.43 (−1.30 to 0.44) |
0.330 |
−1.46 (−2.53 to −0.38) |
0.008 |
−0.15 (−0.27 to −0.02) |
0.025 |
FACT-Lym emotional well-being |
(2†) |
0.69 (0.12–1.25) |
0.018 |
0.80 (0.08–1.52) |
0.030 |
0.02 (−0.08 to 0.11) |
0.738 |
FACT-Lym functional well-being |
2.5 (2–3) |
0.32 (−0.64 to 1.29) |
0.506 |
−1.18 (−2.35 to −0.01) |
0.049 |
−0.21 (−0.35 to −0.08) |
0.002 |
FACT-Lym Lym S |
3 (2.9-5.4) |
1.36 (0.16–2.57) |
0.027 |
1.33 (−0.15 to 2.81) |
0.078 |
−0.004 (−0.18 to 0.17) |
0.961 |
FACT-G Total Score |
3 (3–7) |
0.12 (−2.09 to 2.32) |
0.917 |
−1.79 (−4.50 to 0.92) |
0.194 |
−0.27 (−0.59 to 0.05) |
0.094 |
FACT-Lym TOI‡ |
6 (5.5–11) |
0.94 (−1.46 to 3.34) |
0.439 |
−0.04 (−2.95 to 2.87) |
0.979 |
−0.14 (−0.48 to 0.20) |
0.413 |
FACT-Lym Total Score |
7 (6.5–11.2) |
0.93 (−2.10 to 3.95) |
0.546 |
−0.91 (−4.57 to 2.76) |
0.626 |
−0.26 (−0.68 to 0.16) |
0.224 |
CI, confidence interval; EQ VAS, EQ visual analog scale; Lym S, 15-item Lymphoma Subscale; MID, minimally important difference; TOI, Trial outcome index. |
The EQ VAS overall health score improved over time:
At each visit during treatment, more patients experienced meaningful improvement compared to deterioration; 15% of patients experienced meaningful deterioration, compared with 40% that remained stable, and 45% who experienced meaningful improvement.
Starting from Cycle 3, Day 1, the mean changes from baseline in the EQ VAS were consistently higher than 0 and the minimally important difference improved by at least 40%. This indicates a positive improvement in overall health as early as two cycles into loncastuximab tesirine treatment. The mean change score continually increased to minimally important difference or greater after seven cycles of treatment, and all but one patient at Cycle 8 or later were responders.
Patients who remained at Cycle 9, Day 1 included elderly patients (40% of whom were aged 65 to <75 years, and 20% aged >75 years), and patients who were heavily pretreated (30% with >3 previous treatments).
Regarding patients’ responses to how much they were affected by side effects of treatment at baseline, 81% stated “not at all” or “a little bit,” and 5% claimed “quite a bit” or “very much,” reflecting residual side effects from prior treatments. During treatment with loncastuximab tesirine, >60% of patients reported being “not at all” or “a little bit” bothered by side effects of treatment.
In summary, results from this analysis indicate a benefit in patients with R/R DLBCL who were treated with loncastuximab tesirine, including elderly patients, as the data show that patients remained stable or improved their overall HRQoL, particularly among responders. Most patients reported an improvement in symptoms of pain, lumps/swelling, and weight loss compared with baseline during most visits. Itching was the only symptom—in the whole cohort, including elderly patients—that worsened over time. The majority of patients said the treatment was tolerable. This study has some limitations, including recall bias, but overall, these findings seem promising for loncastuximab tesirine treatment for patients with R/R DLBCL.
Understanding your specialty helps us to deliver the most relevant and engaging content.
Please spare a moment to share yours.
Please select or type your specialty
Your opinion matters
Subscribe to get the best content related to lymphoma & CLL delivered to your inbox