Resources

Chapter 1: r/r DLBCL: Unmet Needs & the ZYNLONTA^® MOA

Hello, I’m here with Dr. Milham Solh, an expert in diffuse large B-cell lymphoma, or DLBCL. In this video we’ll discuss some challenges and unmet needs in the treatment of relapsed or refractory DLBCL, and the role of ZYNLONTA^® in this therapeutic area. Why don’t you start by giving our viewers an overview of relapsed or refractory DLBCL?

I’d be happy to. Diffuse large B-cell lymphoma is the most common subtype of non-Hodgkin’s lymphoma. It represents just about a third of non-Hodgkin lymphoma cases. Diffuse B-cell lymphoma is clinically aggressive, and treatment can be challenging. That’s because at least 40 percent of patients will fail their first-line treatment or will relapse after remission. Now, following that failure or relapse after the first-line therapy, second-line treatment options may be considered. For example, stem cell transplant or SCT is a curative option, but about half of the patients are ineligible because of either advanced age, comorbidities, social and access issues, or individual choice among patients who are eligible for transplant. Less than 15 percent actually receive it, and half of those patients ultimately were relapsed.

Wow, that’s a disheartening statistic. What about third-line treatment?

Third-line treatment is very individualized, and it’s based on various patient and disease related factors. For example, if we take car t cell therapy, it’s a potentially curative option, but there are many obstacles to its success and access. The response remains also not very high, because in a real-world experience, only 16.5 percent of patients receive car t cell therapy in a third-line setting. Also, other studies have shown that up to half of the patients who do receive it may ultimately relapse. Ostensibly an unmet clinical need remains for patients who are ineligible for or who relapse after stem cell transplant or car t cell therapy.

It certainly seems that way!

Well on a positive note, there are many treatment options that are continually evolving and help to address this need.

Well, that’s a perfect segue to ZYNLONTA^®. Why don’t you explain what it is and specifically what is it indicated for.

Sure. ZYNLONTA^® is an antibody drug conjugate for relapsed or refractory diffuse large B-cell lymphoma. ZYNLONTA^® is indicated for the treatment of adult patients who relapsed or are refractory with large B-cell lymphoma after two or more lines of systemic therapy. And that includes diffuse large B-cell lymphoma, not otherwise specified diffuse large B-cell lymphoma arising from a low-grade lymphoma, and high-grade B-cell lymphomas.

And knowing that different approaches to treating relapse or refractory DLBCL are needed, can you tell us how ZYNLONTA^® works?

Of course. So ZYNLONTA^® is the first and only CD19-directed antibody drug conjugate, or what we refer to as ADC. It is approved for diffuse large B-cell lymphoma. Now we know that CD19 is a very important target, but not all CD19 targeted therapies work in the same way. Let me explain how ZYNLONTA^® works. It is composed of a humanized monoclonal antibody that binds to the CD19 receptors on the tumor cells. Once ZYNLONTA^® binds to the CD19, it is internalized into the tumor cell. And unlike other CD19-targeted treatments, there is a unique cytotoxic PBD dimer payload that gets released inside the cell. Now this PBD, which is an alkylating agent, it binds to the DNA minor groove and forms a cytotoxic DNA interstrand crosslinks. This subsequently induces tumor cell death.

Dr Solh, thanks so much for sharing your time and expertise in this area. We hope you found this discussion informative. To see more of our discussion, please watch the other videos available in this series. For additional information, you can visit ZYNLONTAhcp.com or contact your ADC Therapeutic Sales Representative. Now, please take a moment to view the important safety information for ZYNLONTA^®. Thank you.

Chapter 2: LOTIS-2 Study Design

Hello, I’m here with Dr. Milham Solh, an expert in diffuse large B-cell lymphoma, or DLBCL. In this video we’ll discuss the study design and patient population in LOTIS-2, the ZYNLONTA^® registrational trial that led to FDA approval. Dr Solh, I’m sure our viewers are interested in learning about the LOTIS-2 trial. Would you describe the study design?

Of course. LOTIS-2 was a large, open-label, single arm, Phase 2 study. In this study we included 145 adult patients with a relapse or refractory diffuse large B-cell lymphoma who had received two or more prior systemic therapies. I’ll talk more about the patient in just a moment. ZYNLONTA^® was administered as a single agent in 30-minute outpatient infusion every three weeks. The treatment was continued until progressive disease or unacceptable toxicity for up to one year. Now, the primary endpoint of the study was overall response rate, and the key secondary endpoints were duration of response and complete response.

Before you continue, I noticed that ZYNLONTA^® was given as a single agent. Is that meaningful for DLBCL treatment?

You know as a physician I can tell you that the notion of a single agent therapy is important considering these patients. Remember here, we’re talking about a third-line treatment, so patients have already endured multiple lines of therapy, which can typically involve multiagent regimens. Being able to offer the simple dosing schedule of a single 30-minute outpatient infusion once every three weeks is definitely a meaningful component to me.

Yes, it makes a lot of sense. Now what can you tell us about the types of patients who were permitted in the LOTIS-2 study?

The study’s inclusion and exclusion criteria are shown here.

I see. Is there anything about the patients who could be included that stands out to you?

Actually yes. LOTIS-2 permitted the inclusion of patients who are transplant eligible as well as patients who are transplant Ineligible. You can see from the trial it also permitted patients with high-risk tumor characteristics.

So that was the study design. Could you provide details about the patients who ultimately participated in the trial?

Certainly. LOTIS-2 included a broad range of heavily pre-treated patients with difficult to treat disease. The tables that you see on the screen present a select baseline patient and disease characteristics, prior therapies, and refractoriness to prior treatment. This patient population actually reflects the disease’s heterogeneity. I’d like to point out few things in particular that typically make treatment more challenging. For example, 14 of patients were 75 years or older, and the median age on the study was 66. Also, you can see that patients with potentially fast growing and/or aggressive forms of diffuse large B-cell lymphoma were included in the study as well. While the majority of patients had diffuse large B-cell lymphoma not otherwise specified, 20 percent of patients had diffuse large B-cell lymphoma arising from a low-grade lymphoma, and eight percent had high-grade b cell lymphoma. In addition to it, the majority of LOTIS-2 patients had refractory disease, 20 percent were refractory to their initial treatment, and 17 percent were refractory to all prior treatments. Those patients may have been chemosensitive. So, if you took the overall study, 63 percent of patients in the trial had refractory disease.

Thanks for pointing out those specific characteristics. You mentioned in a previous chat that by third-line, these patients have already been through a lot.

We can see evidence of that absolutely. These patients were heavily pre-treated. More than half of them receiving anywhere from three to seven prior lines of therapy with a median number of lines of therapy prior to ZYNLONTA^® were three. Some patients actually had undergone car t cell therapy or a prior transplant and most of them, 71 actually, had not responded to intensive chemotherapy. So clearly there is an extensive unmet need for patients who are ineligible for or who relapse after stem cell transplant or car t cell therapy. It is very important to appreciate the types of patients in LOTIS-2, including those with distinct treatment challenges, because it provides an important context for the results that we saw in this trial. Many patients achieved a meaningful response with ZYNLONTA^® as a single agent. You can learn about those responses in the video focused on LOTIS-2 efficacy results.

That’s right. Dr Sohl, thanks so much for sharing your time and expertise in this area. We hope you found this discussion informative. To see more of our discussion, please watch the other videos available in this series. For additional information, you can visit ZYNLONTAhcp.com or contact your ADC Therapeutic Sales Representative. Now, please take a moment to view the important safety information for ZYNLONTA^®. Thank you.

Chapter 3: LOTIS-2 Response Rates

Hello, I’m here with Dr. Milham Solh, an expert in diffuse large B-cell lymphoma, or DLBCL. In this video we’ll discuss responses seen in LOTIS-2, the ZYNLONTA^® registrational trial. Dr. Solh, before we get into response rates, why don’t you briefly remind us of the LOTIS-2
study design and patient population.

Yes, I’d like to touch on that information because it provides important context for the study results. LOTIS-2 was a large open label, single arm Phase 2 study. It included 145 adult patients with a relapsed or refractory diffuse large B-cell lymphoma who had received two or more prior systemic therapies. ZYNLONTA^® was administered as monotherapy in a 30-minute, outpatient infusion every three weeks. This treatment was continued until progressive disease or unacceptable toxicity for up to one year. The primary end point of the study was overall response rate, but the main key secondary endpoints were duration of response and complete response. LOTIS-2 included a broad range of heavily pre-treated patients with difficult to treat disease as outlined here.

Thank you for the reminder of those important details. With that context in mind, let’s discuss the results.

Sure. So, the data cut-off date for LOTIS-2 was April 6, 2020. Patients had been followed for a median of 7.3 months and the range was anywhere from 0.3 to 20.2 months. By the cut-off date, nearly half of LOTIS-2 patients, and to be very specific 48.3 percent, achieved a meaningful response with ZYNLONTA^® as a single agent therapy. Half of those patients who responded, or 24.1 percent of all study patients, achieved a complete response, and half achieved a partial response. Importantly, not only did many patients achieve a response, but the median time to response was rapid: 1.3 months for the overall response. The median time to a complete response was 1.4 months. So, by the first imaging assessment, which was performed approximately six weeks into treatment, a substantial number of patients who responded to ZYNLONTA^® had already done so.

And how long did those responses last at the time of the data cut off?

The median duration of overall response was 10.3 months, and the median duration of complete response was 13.4 months.

Thank you is there anything you’d like to add about the responses seen in the trial?

I’d just like to emphasize that it’s extremely important to consider the responses in this patient population as we discussed, because most of these patients were heavily pre-treated and had distinct treatment challenges. As we’re addressing the types of patients included in LOTIS-2, we can actually dig deeper into the response rates. The study investigators analyzed the response data by patient subgroup. This can be very helpful when physicians are making clinical decisions about their own patients. Now bear in mind that these were exploratory analysis, or predefined subgroups. The study was not powered to demonstrate an effect in patient subgroups, and the sample sizes were small. That being said, responses were seen in trial participants regardless of age, disease subtype, level of refractoriness, number of prior lines of therapy, or treatment history. This includes patients who had prior car t cell therapy, had prior stem cell transplant, or were refractory to all prior therapies. A pervasive unmet clinical need remains for patients who are ineligible for or who relapse after stem cell transplant or car t cell therapy. The fact that responses within long term were seen among these patients should not go unnoticed. And remember these responses were observed with a single agent infusion only once every three weeks.

Thanks for such a detailed review. I’m sure our viewers appreciate seeing the responses by patient subgroup. Now I understand all the responses you just described were from the primary analysis, and the follow-up analysis was performed.

Yes. The data cut-off date for primary analysis was April of 2020. The follow-up analysis extended to March of 2021. This allowed us immediate follow-up time of 7.8 months whereas the median follow-up time for the primary analysis was 7.3 months. If you recall the overall response rate was the primary endpoint of the study and the follow-up analysis overall response rate had not changed from the original; it remained at 48.3 percent. There were slight variations to the complete remission and partial remission rates. One additional patient had achieved a complete remission which increased the CR rate from 24.1 to 24.8 percent so the PR rate decreased slightly from 24.1 percent to 23.4 percent.

Interesting. Did the follow-up analysis evaluate duration of response?

Indeed, it did. If you recall from the primary analysis we mentioned earlier, median duration of overall response to ZYNLONTA^® had been 10.3 months. With the additional follow-up time that median increased to 13.4 months. For complete remissions achieved, the median duration of response from the primary analysis had been 13.4 months with the additional follow-up time the median for complete remissions was not reached.

Were any new safety concerns identified in the follow-up analysis at the time of follow-up?

No new safety concerns had been reported.

I’m glad to hear that. Thanks so much for addressing the follow-up analysis. I have one more question. Did any of the trial participants with disease progression receive subsequent treatment?

Yes. Actually some patients went on to receive other anti-cancer therapy after ZYNLONTA^® including 15 patients who received car t-cell therapy and nine patients who went on to receive a transplant. The clinical outcomes for those patients have not been confirmed in a randomized clinical trial.

Dr. Sohl, thanks so much for sharing your time and expertise in this area. We hope you found this discussion informative. To see more of our discussion, please watch the other videos available in this series. For additional information, you can visit ZYNLONTAhcp.com or contact your ADC Therapeutic Sales Representative. Now, please take a moment to view the important safety information for ZYNLONTA^®. Thank you.

Chapter 4: ZYLONTA^® Safety Profile

Hello, I’m here with Dr. Milham Solh, an expert in diffuse large B-cell lymphoma, or DLBCL. In this video we’ll discuss the safety profile of ZYNLONTA^®. Dr. Solh, I understand the safety and tolerability of a therapeutic option is of great importance to patients. What can you tell us about the safety profiles in ZYNLONTA^®?

You’re absolutely right. The significance of safety and tolerability for both the patient experience and the ability to follow the chosen treatment plan cannot be overstated. As we consider this information, it’s important to remember that patients were heavily pre-treated and had difficult to treat disease. For example, in LOTIS-2 patients had received two to seven prior lines of therapy, with a median of three lines of therapy. The median age was also increased at 66 years and 14 percent of patients were age 75 or older. So, if you look at the study design, the treatment continued until progressive disease or unacceptable toxicity for up to one year. The table here presents the adverse reactions including any grade of adverse reactions that occurred in at least 10 percent of LOTIS-2 participants. You can see the incidence of a grade three or four adverse reactions is also shown.

I see. That’s leads me to my next question. Do patients experience any serious adverse reactions?

Yes. Serious adverse reactions occurred in 28 percent of the patients. If we look at the most common serious adverse reactions that occurred in more than two percent of the patients, these were febrile neutropenia, pneumonia edema pleural effusion, and sepsis. There were fatal adverse reactions that occurred in one percent, and this was mainly due to infection. As far as permanent treatment discontinuation due to an adverse reaction, this occurred in 19 percent of patients. Adverse reactions that resulted in permanent discontinuation, in more than two percent of the patients these were an increased gamma GT edema and effusion. Now if we continue on the safety results from the LOTIS-2 trial, you can see the select lab abnormalities that occurred in at least 10 percent of the patients.

Yes, Dr. Solh. Were there any adverse reactions that require dose interruption?

As a matter of fact, there were. Throughout the LOTIS-2 studies, the ZYNLONTA^® dosage was interrupted for an adverse reaction. In 49 of the patients for things such as increased gamma GT, neutropenia thrombocytopenia, and edema being the most common events. The ZYNLONTA^® dose was reduced for an adverse reaction in 8 percent of the patients with increased gamma GT, the most common event. Here I’d like to point out that the longer full prescriber information provides recommendations for those delays and modifications to address an adverse event.

Is it notable that there were no differences in safety or effectiveness between older and younger patients in LOTIS-2?

This is a very important finding as many patients with relapsed or refractory diffuse large B-cell lymphoma are older. As we can see in the LOTIS-2 trials, the median age was 66 and 14 of the patients were more than 75 years of age. The information you just shared is undoubtedly helpful to our viewers and I’m wondering if we can provide even more details from the LOTIS-2 trial to help prepare care teams regarding ZYNLONTA^® safety and tolerability. I think it’d be valuable to know how specific adverse reactions were addressed.

I agree. Although each patient’s circumstances and response to treatment are unique, this type of information would be very beneficial to care providers. So, let’s take a look at the recommended dose management of particular adverse reactions and the ZYNLONTA^® full prescriber information, and how to those modify based on what was been done in the LOTIS-2 study. The adverse events we’ll look at are effusion and edema myelosuppression, infections, and cutaneous reactions. So, these are potentially serious adverse reactions that were seen with ZYNLONTA^® treatment, and most are included in the warnings and precautions section of the PI. Here you can see the recommendations derived from the ZYNLONTA® prescribing information for managing effusion and edema. And this includes the use of dexamethasone premedication, for example, to reduce the incidence of PPD-related adverse reactions such as effusion, edema, and liver function test abnormalities. Now let’s see the management of these adverse events and the LOTIS-2 study. As you see here, this is the incidence of those delays, reductions, and withdrawals for effusion and edema. Based on the study protocol, dosage delays due to any adverse reactions were made before those reductions, and the incidence of delays were always higher.

Thanks, this is very helpful. I imagine our viewers are interested in learning about management of myelosuppression. Could you address that next?

Of course. Let’s again begin with the recommendations derived from the ZYNLONTA^® prescribing information. Regarding myelosuppression, prophylactic granulocyte colony stimulating factor administration may be considered as applicable here. I’d like to point out that the longer full prescriber information provides recommendations for those delays and modifications to address an adverse event. As for dosing, this chart presents the recommended dose modifications for neutropenia and thrombocytopenia. Now let’s look at the dose management of myelosuppression and the LOTIS-2 trial. Here you can see the incidence of those delays, reductions, and withdrawals for neutropenia, thrombocytopenia, and anemia.

Very interesting. As you mentioned before, I see that dosage delays were more frequent than dose reductions. So, let’s move on. Why don’t we address infections next?

Okay. So, the table on the screen here presents recommendations derived from ZYNLONTA^® prescribing information. The recommended dose modifications for infections are shown here. See that again, if dosing is delayed by more than three weeks due to toxicity related to ZYNLONTA^®, subsequent doses should be reduced by 50 percent. And then, if the toxicity recurs, treatment discontinuation should be considered.

Yes, that’s very correct. This is the guidance for all of the adverse reactions we’ll be discussing today.

Now let’s look at the dose management of infection and the LOTIS-2 trial. This chart here shows you the incidence of those delays, reductions, and withdrawals for infection. And this includes but is not limited to upper respiratory tract infection such as upper respiratory tract congestion, respiratory tract nasopharyngitis, rhinitis rhinoviral infection and sinusitis.

Thanks for that. Again, I’m sure this information is helpful to those wanting to know more about ZYNLONTA^® safety and tolerability. Let’s take a look at cutaneous reactions next.

Certainly. The table on the screen here presents the recommendations derived from ZYNLONTA^® prescribing information. Let’s review the guidance on those modifications. You can see that there are recommendations specific to photosensitivity and rash. Now, if we look at those management of cutaneous reactions and LOTIS-2, as you can see here, the incidence of those delays, reductions, and withdrawals for cutaneous reactions, these data are broken out into photosensitivity cutaneous reactions and non-photosensitivity cutaneous reactions. Now in case anyone is wondering what comprised cutaneous reactions, that would be rash including those listed beneath the table, pruritus and photosensitivity reaction.

I’m sure someone was wondering so thanks for the explanation and thanks for going through all of those details. Safety information is so important.

I couldn’t agree more. You know as a prescribing physician I find those data very helpful, so hopefully our viewers will, too. I’d also like to know that clinicians should refer to the ZYNLONTA^® prescribing information for guidance on addressing other adverse reactions as well. What’s important to take away from this is that although LOTIS-2 investigators were able to address some of the adverse reactions reported here, you should always prioritize ZYNLONTA^® PI recommendations as you manage patient care.

Dr. Sohl, thanks so much for sharing your time and expertise in this area. We hope you found this discussion informative. To see more of our discussion, please watch the other videos available in this series. For additional information, you can visit ZYNLONTAhcp.com or contact your ADC Therapeutic Sales Representative. Now, please take a moment to view the important safety information for ZYNLONTA^®. Thank you.

Chapter 5: ZYNLONTA^® Dosing

Hello, I’m here with Dr. Milham Solh, an expert in diffuse large B-cell lymphoma, or DLBCL. In this video we’ll discuss ZYNLONTA^® dosing and administration. Dr. Sohl, let’s start with the basic question: how is ZYNLONTA^® given to patients?

ZYNLONTA^® offers patients a simple dose and schedule. It’s given as a single 30-minute IV infusion that’s given every three weeks. The ZYNLONTA^® infusion may be given in the inpatient or outpatient setting. Administration at a specialized center is not required.

Is the fact that it’s a single agent important?

In my experience it is an important consideration for patients in their third-line of therapy. Remember they’ve already endured two prior treatments, which are typically multi-agent regimens, and everything associated with them. In some cases, patients have received more than two prior treatments, as was the case for many patients in LOTIS-2, the ZYNLONTA^® pivotal trial. So being able to give patients a single-agent treatment every three weeks, and a 30-minute infusion, is definitely a plus.

I understand completely. Now prescribers watching this video would likely want to know the recommended dose of ZYNLONTA^®?

So, the recommended dose of ZYNLONTA^® is 0.15 milligrams per kilogram for the first two cycles, and then with those reduced to 0.075 milligram per kilogram for subsequent cycles. In LOTIS-2, ZYNLONTA^® was administered until progressive disease or acceptable toxicity. It’s very important to note that pre-medication with dexamethasone is recommended to help reduce the incidence and severity of adverse reactions related to the PBD dimer, the cytotoxic payload for ZYNLONTA^®. The recommended dose for dexamethasone is
four milligrams. You can give it oral or IV twice daily for three days beginning the day before the infusion unless there is a
contraindication.

Dr. Solh, if a patient has an adverse reaction during ZYNLONTA^® treatment, should the dose be modified?

The ZYNLONTA^® full prescribing information provides recommendations for those delays modifications to address any adverse reactions based on its severity. As shown in this table, dosage delays are recommended as the initial measure to allow toxicities of a particular grade to resolve. If a dosing is delayed by more than three weeks due to a toxicity related to ZYNLONTA^®, the subsequent dose should be reduced by 50 percent. Now at that point if the toxicity recurs following those reductions, discontinuation should be considered. And please note, if toxicity requires those reductions following the second dose of 0.15 milligrams per kilogram, which is cycle 2, the patient should receive that dose of 0.075 milligram per kilogram for cycle 3.

I suppose my last question about dosing is this: based on the types of patients receiving ZYNLONTA^®, and common dosing and administration related challenges for patients with relapsed or refractory DLBCL, how often would the ZYNLONTA^® dosing schedule be a major factor in treatment decisions?

So, in my opinion, and speaking from my own experience as a physician, I would consider the ZYNLONTA^® dosing schedule a very meaningful and beneficial feature in this category, and in particular for this patient population. For that reason, it would almost always factor into new treatment decisions for such patient population.

Dr. Sohl, thanks so much for sharing your time and expertise in this area. We hope you found this discussion informative. To see more of our discussion, please watch the other videos available in this series. For additional information, you can visit ZYNLONTAhcp.com or contact your ADC Therapeutic Sales Representative. Now, please take a moment to view the important safety information for ZYNLONTA^®. Thank you.

Chapter 6: ZYNLONTA^® FAQs

Hello, I’m here with Dr. Milham Solh, an expert in diffuse large B-cell lymphoma, or DLBCL. In this video we’ll discuss some practical considerations related to frequently asked questions regarding ZYNLONTA^®. Dr. Sohl, the first question has to do with patient selection. For whom should ZYNLONTA^® be considered?

To address patient types, let’s talk about the participants in LOTIS-2, which was a ZYNLONTA^® pivotal trial. As shown here, LOTIS-2 included a broad range of heavily pre-treated patients with difficult to treat disease, such as patients with intensive salvage therapy failure, refractory disease, 2 to 7 lines of prior therapies, and large B-cell lymphoma arising from low-grade lymphoma and high-grade B-cell lymphoma. The overall response rate was 48.3 percent and half of those patients or 24.1 percent of all patients they achieved a complete response. When we did an explanatory analysis to look at responses and select patient subgroups, such as patients with diffuse large B-cell lymphoma arising from low-grade lymphoma, or patients with high-grade B-cell lymphomas, patients with prior stem cell transplant, prior car t cell therapy and any patients with refractory disease, overall responses were observed regardless of age, disease type level or refractoriness, number of prior lines of therapy, or treatment history. And remember, these responses were observed with a single-agent infusion once every three weeks.

Thanks, that should be very helpful to prescribing physicians. Okay, another common question is can ZYNLONTA^® be used after another CD19-directed therapy?

That’s actually a great question and the answer to your question is yes. But I’d like to note that there are no specific clinical recommendations for transitioning between CD19-targeted therapies. In the LOTIS-2 trial, 9 patients had received CD19-directed car t cell therapy prior to treatment with ZYNLONTA^®. Those participants were required to have confirmed CD19 expression before they received their ZYNLONTA^® therapy. Although CD19 testing is not required for ZYNLONTA^® use, the response rate for those patients was 46.2 percent including two patients with a complete response.

That’s good to know. A follow-up question is, has ZYNLONTA^® been used before another CD19-directed therapy?

Well in the LOTIS-2 study, 15 patients went on to receive subsequent cart t cell therapy after disease progression. And these cases ZYNLONTA^® was not used as a bridge. The safety and efficacy outcomes for those patients have not been confirmed in a randomized clinical trial. Just note that the impact of the diffuse B-cell lymphoma treatment on CD19 expression levels has not been fully elicited.

The next two questions are a little more patient-focused. First how should health care providers counsel patients. Are there specific topics that should be discussed?

I appreciate this question. You know, it’s important to set expectations with patients and their caregivers before treatment is initiated. The ZYNLONTA^® full prescribing information includes specific counseling points that you’ll see projected here. As you can see, physicians are encouraged to counsel patients about effusion and edema, about myelosuppression infections, cutaneous reactions, and embryo fetal toxicity and lactation. Patients should also be advised to read the FDA-approved patient labeling or patient information, which provides more details about what ZYNLONTA^® is and what patients should tell their doctor before receiving ZYNLONTA^®, and what to expect from therapy. Thank you, Doctor. And if I may take a moment to tell our viewers about the robust patient support program available to eligible patients who are prescribed ZYNLONTA^®. I understand it offers personalized assistance from ADC Therapeutics. Dedicated case managers and nurses can provide the support needed to help patients get started and stay on ZYNLONTA^® therapy. Patients and their caregivers can ask questions, discuss concerns, and get some guidance in addition to financial support. Prescribing physicians who want to learn more about the program associated with ZYNLONTA^® can call Advancing Patient Support at the number on the screen or visit advancingpatientsupport.com.

Dr. Sohl, thanks so much for sharing your time and expertise in this area. We hope you found this discussion informative. To see more of our discussion, please watch the other videos available in this series. For additional information, you can visit ZYNLONTAhcp.com or contact your ADC Therapeutic Sales Representative. Now, please take a moment to view the important safety information for ZYNLONTA^®. Thank you.